The role of Ca2+ signaling in Parkinson's disease

DMM Disease Models and Mechanisms

Volumn 10, Issue 5, 2017, Pages 519-535

  Zaichick, Sofia V ^a   McGrath, Kaitlyn M ^a   Caraveo, Gabriela ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

A synuclein; Calcium; Parkinson's disease

Indexed keywords

CALCIUM ION; CALCIUM;

CALCIUM CELL LEVEL; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; CALCIUM TRANSPORT; CELL MEMBRANE; CELL ORGANELLE; CYTOSOL; ENDOPLASMIC RETICULUM; GOLGI COMPLEX; HUMAN; LYSOSOME; MITOCHONDRION; NEUROPATHOLOGY; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; METABOLISM;

CALCIUM; CALCIUM SIGNALING; HUMANS; ORGANELLES; PARKINSON DISEASE;

EID: 85019558668     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.028738     Document Type: Review

References (313)

1. Albert, K. A., Helmer-Matyjek, E., Nairn, A. C., Muller, T. H., Haycock, J. W., Greene, L. A., Goldstein, M. and Greengard, P. (1984). Calcium/phospholipid-dependent protein kinase (protein kinase C) phosphorylates and activates tyrosine hydroxylase. Proc. Natl. Acad. Sci. USA 81, 7713-7717.
2. Allen, A. S. and Satten, G. A. (2009). A novel haplotype-sharing approach for genome-wide case-control association studies implicates the calpastatin gene in Parkinson's disease. Genet. Epidemiol. 33, 657-667.
3. Allen, A. S. and Satten, G. A. (2010). SNPs in CAST are associated with Parkinson disease: a confirmation study. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 973-979.
4. Alvira, D., Ferrer, I., Gutierrez-Cuesta, J., Garcia-Castro, B., Pallas, M. and Camins, A. (2008). Activation of the calpain/cdk5/p25 pathway in the girus cinguli in Parkinson's disease. Parkinsonism Relat. Disord. 14, 309-313.
5. Angelova, P. R., Ludtmann, M. H. R., Horrocks, M. H., Negoda, A., Cremades, N., Klenerman, D., Dobson, C. M., Wood, N. W., Pavlov, E. V., Gandhi, S. et al. (2016). Ca2+ is a key factor in alpha-synuclein-induced neurotoxicity. J. Cell Sci. 129, 1792-1801.
6. Arispe, N., Pollard, H. B. and Rojas, E. (1993). Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1-40)] in bilayer membranes. Proc. Natl. Acad. Sci. USA 90, 10573-10577.
7. Augustine, G.J., Santamaria, F. and Tanaka, K. (2003). Local calcium signaling in neurons. Neuron 40, 331-346.
8. Bahar, E., Kim, H. and Yoon, H. (2016). ER stress-mediated signaling: action potential and Ca(2+) as key players. Int. J. Mol. Sci. 17, 1558.
9. Baimbridge, K. G., Celio, M.R.and Rogers, J. H.(1992). Calcium-binding proteins in the nervous system. Trends Neurosci. 15, 303-308.
10. Baratier, J., Peris, L., Brocard, J., Gory-Faure, S., Dufour, F., Bosc, C., Fourest-Lieuvin, A., Blanchoin, L., Salin, P., Job, D. et al. (2006). Phosphorylation of microtubule-associated protein STOP by calmodulin kinase II. J. Biol. Chem. 281, 19561-19569.
11. Beal, M. F. Oakes, D. Shoulson, I. Henchcliffe, C. Galpern, W. R. Haas, R. Juncos, J. L. Nutt, J. G. Voss, T. S. Ravina, B. et al. (2014). A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 71, 543-552.
12. Bean, B. P. (2007). Neurophysiology: stressful pacemaking. Nature 447, 1059-1060.
13. Beavan, M. S. and Schapira, A. H. V. (2013). Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. Ann. Med. 45, 511-521.
14. Becker, C., Jick, S. S. and Meier, C. R. (2008). Use of antihypertensives and the risk of Parkinson disease. Neurology 70, 1438-1444.
15. Bedford, C., Sears, C., Perez-Carrion, M., Piccoli, G. and Condliffe, S. B. (2016). LRRK2 Regulates Voltage-Gated Calcium Channel Function. Front. Mol. Neurosci. 9, 35.
16. Benes, F. M. and Berretta, S. (2001). GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25, 1-27.
17. Berger, S. M. and Bartsch, D. (2014). The role of L-type voltage-gated calcium channels Cav1.2 and Cav1.3 in normal and pathological brain function. Cell Tissue Res. 357, 463-476.
18. Berridge, M. J. (2005). Unlocking the secrets of cell signaling. Annu. Rev. Physiol. 67, 1-21.
19. Berridge, M. J., Lipp, P. and Bootman, M. D. (2000). The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1, 11-21.
20. Berridge, M. J., Bootman, M. D. and Roderick, H. L. (2003). Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4, 517-529.
21. Bezprozvanny, I. (2009). Calcium signaling and neurodegenerative diseases. Trends Mol. Med. 15, 89-100.
22. Bezprozvanny, I. B. (2010). Calcium signaling and neurodegeneration. Acta Naturae 2, 72-82.
23. Binukumar, B. K. and Pant, H. C. (2016). TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson's disease. Neural Regen. Res. 11, 698-701.
24. Binukumar, B. K., Shukla, V., Amin, N. D., Grant, P., Bhaskar, M., Skuntz, S., Steiner, J. and Pant, H. C.(2015). Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson's disease. Mol. Biol. Cell 26, 4478-4491.
25. Bollo, M., Paredes, R. M., Holstein, D., Zheleznova, N., Camacho, P. and Lechleiter, J. D. (2010). Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs. PLoS ONE 5, e11925.
26. Bootman, M. D. (2012). Calcium signaling. Cold Spring Harb. Perspect. Biol. 4, a011171.
27. Bootman, M. D., Lipp, P. and Berridge, M. J. (2001). The organisation and functions of local Ca(2+) signals. J. Cell Sci. 114, 2213-2222.
28. Bose, A. and Beal, M. F. (2016). Mitochondrial dysfunction in Parkinson's disease. J. Neurochem. 139 Suppl. 1, 216-231.
29. Braak, H., Ghebremedhin, E., Rub, U., Bratzke, H. and Del Tredici, K. (2004). Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 318, 121-134.
30. Brown, T. P., Rumsby, P. C, Capleton, A. C, Rushton, L. and Levy, L. S. (2006). Pesticides and Parkinson's disease-is there a link? Environ. Health Perspect. 114, 156-164.
31. Bruzzone, S., Kunerth, S., Zocchi, E., De Flora, A. and Guse, A. H. (2003). Spatio-temporal propagation of Ca2+ signals by cyclic ADP-ribose in 3T3 cells stimulated via purinergic P2Y receptors. J. Cell Biol. 163, 837-845.
32. Burgoyne, R. D. (2007). Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling. Nat. Rev. Neurosci. 8, 182-193.
33. Burre, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M. R. and Sudhof, T. C. (2010). Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329, 1663-1667.
34. Buttner, S., Faes, L., Reichelt, W. N., Broeskamp, F., Habernig, L., Benke, S., Kourtis, N., Ruli, D., Carmona-Gutierrez, D., Eisenberg, T. et al. (2013). The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to alpha-synuclein toxicity in Parkinson's disease models. Cell Death Differ. 20, 465-477.
35. Calì, T., Ottolini, D. and Brini, M. (2011). Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease. Biofactors 37, 228-240.
36. Calì, T., Ottolini, D. and Brini, M. (2012a). Mitochondrial Ca(2+) and neurodegeneration. Cell Calcium 52, 73-85.
37. Calì, T., Ottolini, D., Negro, A. and Brini, M. (2012b). alpha-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J. Biol. Chem. 287, 17914-17929.
38. Calì, T., Ottolini, D., Negro, A. and Brini, M. (2013). Enhanced parkin levels favor ER-mitochondria crosstalk and guarantee Ca(2+) transfer to sustain cel bioenergetics. Biochim. Biophys. Acta 1832, 495-508.
39. Calì, T., Ottolini, D. and Brini, M. (2014). Calcium signaling in Parkinson's disease. Cell Tissue Res. 357, 439-454.
40. Carafoli, E. (2002). Calcium signaling: a tale for all seasons. Proc. Natl. Acad. Sci. USA 99, 1115-1122.
41. Caraveo, G., Auluck, P. K., Whitesell, L., Chung, C. Y., Baru, V., Mosharov, E. V., Yan, X., Ben-Johny, M., Soste, M., Picotti, P. et al. (2014). Calcineurin determines toxic versus beneficial responses to alpha-synuclein. Proc. Natl. Acad. Sci. USA 111, E3544-E3552.
42. Carrasco, M. A. and Hidalgo, C. (2006). Calcium microdomains and gene expression in neurons and skeletal muscle cells. Cell Calcium 40, 575-583.
43. Celardo, I., Costa, A. C, Lehmann, S., Jones, C, Wood, N., Mencacci, N. E., Mallucci, G. R., Loh, S. H. Y. and Martins, L. M. (2016). Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease. Cell Death Dis. 7, e2271.
44. Chagniel, L, Robitaille, C, Lebel, M. and Cyr, M. (2012). Striatal inhibition of calpains prevents levodopa-induced neurochemical changes and abnormal involuntary movements in the hemiparkinsonian rat model. Neurobiol. Dis. 45, 645-655.
45. Chalovich, E. M., Zhu, J.-H., Caltagarone, J., Bowser, R. and Chu, C. T. (2006). Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J. Biol. Chem. 281, 17870-17881.
46. Chan, E. Y., Tang, T., Tu, H., Maximov, A., Wang, Z., Wellington, C. L., Hayden, M. R. and Bezprozvanny, I. (2003). Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1, 4, 5) triphosphate receptor type 1. Am. J. Hum. Genet. 73, 561-561.
47. Chan, C. S., Guzman, J. N., Ilijic, E., Mercer, J. N., Rick, C, Tkatch, T., Meredith, G. E. and Surmeier, D. J. (2007). 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 447, 1081-1086.
48. Chaudhuri, K. R., Healy, D. G. and Schapira, A. H. V. (2006). Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 5 235-245.
49. Chen, Y. P., Song, W., Huang, R., Chen, K., Zhao, B., Li, J., Yang, Y. and Shang, H.-F. (2013). GAK rs1564282 and DGKQ rs11248060 increase the risk for Parkinson's disease in a Chinese population. J. Clin. Neurosci. 20, 880-883.
50. Chergui, K., Svenningsson, P. and Greengard, P. (2004). Cyclin-dependent kinase 5 regulates dopaminergic and glutamatergic transmission in the striatum. Proc. Natl. Acad. Sci. USA 101, 2191-2196.
51. Chin, D. and Means, A. R. (2000). Calmodulin: a prototypical calcium sensor. Trends Cell Biol. 10, 322-328.
52. Choi, B.-K., Choi, M.-G., Kim, J.-Y., Yang, Y., Lai, Y., Kweon, D.-H., Lee, N. K. and Shin, Y.-K. (2013). Large alpha-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proc. Natl. Acad. Sci. USA 110, 4087-4092.
53. Christensen, K. A., Myers, J. T. and Swanson, J. A. (2002). pH-dependent regulation of lysosomal calcium in macrophages. J. Cell Sci. 115, 599-607.
54. Churchill, G. C, Okada, Y., Thomas, J. M., Genazzani, A. A., Patel, S. and Galione, A. (2002). NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs. Cell111, 703-708.
55. Clapham, D. E. (2007). Calcium signaling. Cell 131, 1047-1058.
56. Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F. et al. (2006). Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313, 324-328.
57. Copanaki, E., Schurmann, T., Eckert, A., Leuner, K., Muller, W. E., Prehn, J. H. M. and Kogel, D. (2007). The amyloid precursor protein potentiates CHOP induction and cell death in response to ER Ca2+ depletion. Biochim. Biophys. Acta 1773, 157-165.
58. Coultrap, S. J. and Bayer, K. U. (2012). CaMKII regulation in information processing and storage. Trends Neurosci. 35, 607-618.
59. Crocker, S. J., Smith, P. D., Jackson-Lewis, V., Lamba, W. R., Hayley, S. P., Grimm, E., Callaghan, S. M., Slack, R. S., Melloni, E., Przedborski, S. et al. (2003). Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease. J. Neurosci. 23, 4081-4091.
60. Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T. and Sulzer, D. (2004). Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305, 1292-1295.
61. Czapski, G. A., Ga?ssowska, M., Wilkaniec, A., Cieslik, M. and Adamczyk, A. (2013). Extracellular alpha-synuclein induces calpain-dependent overactivation of cyclin-dependent kinase 5 in vitro. FEBS Lett. 587, 3135-3141.
62. Damier, P., Hirsch, E. C., Agid, Y. and Graybiel, A.M. (1999). The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 122, 1437-1448.
63. Danzer, K. M., Haasen, D., Karow, A. R., Moussaud, S., Habeck, M., Giese, A., Kretzschmar, H., Hengerer, B. and Kostka, M. (2007). Different species of alpha-synuclein oligomers induce calcium influx and seeding. J. Neurosci. 27, 9220-9232.
64. Dauer, W. and Przedborski, S. (2003). Parkinson's disease: mechanisms and models. Neuron 39, 889-909.
65. Dehay, B., Martinez-Vicente, M., Caldwell, G. A., Caldwell, K. A., Yue, Z., Cookson, M. R., Klein, C., Vila, M. and Bezard, E. (2013). Lysosomal impairment in Parkinson's disease. Mov. Disord. 28, 725-732.
66. Di Fonzo, A., Chien, H. F., Socal, M., Giraudo, S., Tassorelli, C., Iliceto, G., Fabbrini, G., Marconi, R., Fincati, E., Abbruzzese, G. et al. (2007). ATP13A2 missense mutationsinjuvenile parkinsonism and young onset Parkinson disease. Neurology 68, 1557-1562.
67. Di Fonzo, A., Dekker, M. C. J., Montagna, P., Baruzzi, A., Yonova, E. H., Correia Guedes, L., Szczerbinska, A., Zhao, T., Dubbel-Hulsman, L. O. M., Wouters, C. H. et al. (2009). FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology 72, 240-245.
68. Di Scala, C., Yahi, N., Boutemeur, S., Flores, A., Rodriguez, L., Chahinian, H. and Fantini, J. (2016). Common molecular mechanism of amyloid pore formation by Alzheimer's beta-amyloid peptide and alpha-synuclein. Sci. Rep. 6, 28781.
69. Diepenbroek, M., Casadei, N., Esmer, H., Saido, T. C., Takano, J., Kahle, P. J., Nixon, R. A., Rao, M. V., Melki, R., Pieri, L. et al. (2014). Overexpression of the calpain-specific inhibitor calpastatin reduces human alpha-Synuclein processing, aggregation and synaptic impairment in [A30P]alphaSyn transgenic mice. Hum. Mol. Genet. 23, 3975-3989.
70. Dineley, K. T., Hogan, D., Zhang, W.-R. and Taglialatela, G. (2007). Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. Neurobiol. Learn. Mem. 88, 217-224.
71. Dragicevic, E., Poetschke, C., Duda, J., Schlaudraff, F., Lammel, S., Schiemann, J., Fauler, M., Hetzel, A., Watanabe, M., Lujan, R. et al. (2014). Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons. Brain 137, 2287-2302.
72. Dreses-Werringloer, U., Lambert, J.-C., Vingtdeux, V., Zhao, H., Vais, H., Siebert, A., Jain, A., Koppel, J., Rovelet-Lecrux, A., Hannequin, D. et al. (2008). A polymorphism in CALHM1 influences Ca2+ homeostasis, A beta levels, and Alzheimer's disease risk. Cell 133, 1149-1161.
73. Drion, G., Massotte, L., Sepulchre, R. and Seutin, V. (2011). How modeling can reconcile apparently discrepant experimental results: the case of pacemaking in dopaminergic neurons. PLoS Comput. Biol. 7, e1002050.
74. Dryanovski, D. I., Guzman, J. N., Xie, Z., Galteri, D. J., Volpicelli-Daley, L. A., Lee, V. M.-Y., Miller, R. J., Schumacker, P. T. and Surmeier, D. J. (2013). Calcium entry and alpha-synuclein inclusions elevate dendritic mitochondrial oxidant stress in dopaminergic neurons. J. Neurosci. 33, 10154-10164.
75. Dufty, B. M., Warner, L. R., Hou, S. T., Jiang, S. X., Gomez-Isla, T., Leenhouts, K. M., Oxford, J. T., Feany, M. B., Masliah, E. and Rohn, T. T. (2007). Calpain-cleavage of alpha-synuclein: connecting proteolytic processing to disease-linked aggregation. Am. J. Pathol. 170, 1725-1738.
76. Exner, N., Lutz, A. K., Haass, C. and Winklhofer, K. F. (2012). Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. EMBO J. 31, 3038-3062.
77. Fernandez-Suarez, D., Celorrio, M., Lanciego, J. L., Franco, R. and Aymerich, M. S. (2012). Loss of parvalbumin-positive neurons from the globus pallidus in animal models of Parkinson disease. J. Neuropathol. Exp. Neurol. 71, 973-982.
78. Finbow, M. E. and Harrison, M. A. (1997). The vacuolar H+-ATPase: a universal proton pump of eukaryotes. Biochem. J. 324, 697-712.
79. Fitzpatrick, P. F. (1999). Tetrahydropterin-dependent amino acid hydroxylases. Annu. Rev. Biochem. 68, 355-381.
80. Fluegge, D., Moeller, L. M., Cichy, A., Gorin, M., Weth, A., Veitinger, S., Cainarca, S., Lohmer, S., Corazza, S., Neuhaus, E. M. et al. (2012). Mitochondrial Ca(2+) mobilization is a key element in olfactory signaling. Nat. Neurosci. 15, 754-762.
81. Fokina, A. V., Chechenova, M. B., Karginov, A. V., Ter-Avanesyan, M. D. and Agaphonov, M. O. (2015). Genetic evidence for the role of the vacuole in supplying secretory organelles with Ca2+ in Hansenula polymorpha. PLoS ONE 10, e0145915.
82. Follett, J., Darlow, B., Wong, M. B., Goodwin, J. and Pountney, D. L. (2013). Potassium depolarization and raised calcium induces alpha-synuclein aggregates. Neurotox. Res. 23, 378-392.
83. Frei, B. and Richter, C. (1986). N-methyl-4-phenylpyridine (MMP+) together with 6-hydroxydopamine or dopamine stimulates Ca2+ release from mitochondria. FEBS Lett. 198, 99-102.
84. Fujibayashi, A., Taguchi, T., Misaki, R., Ohtani, M., Dohmae, N., Takio, K., Yamada, M., Gu, J., Yamakami, M., Fukuda, M. et al. (2008). Human RME-8 is involved in membrane trafficking through early endosomes. Cell Struct. Funct. 33, 35-50.
85. Fujita, Y., Ohama, E., Takatama, M., Al-Sarraj, S. and Okamoto, K. (2006). Fragmentation of Golgi apparatus of nigral neurons with alpha-synuclein-positive inclusions in patients with Parkinson's disease. Acta Neuropathol. 112, 261-265.
86. Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S. and Obata, F. (2002). A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann. Neurol. 51, 296-301.
87. Gandhi, S., Wood-Kaczmar, A., Yao, Z., Plun-Favreau, H., Deas, E., Klupsch, K., Downward, J., Latchman, D. S., Tabrizi, S.J., Wood, N.W. et al. (2009). PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol. Cell 33, 627-638.
88. Gellerich, F. N., Gizatullina, Z., Gainutdinov, T., Muth, K., Seppet, E., Orynbayeva, Z. and Vielhaber, S. (2013). The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal. IUBMB Life 65, 180-190.
89. Ghanbari, M., Darweesh, S. K. L., de Looper, H. W. J., van Luijn, M. M., Hofman, A., Ikram, M. A., Franco, O. H., Erkeland, S. J.and Dehghan, A. (2016). Genetic variants in MicroRNAs and their binding sites are associated with the risk of Parkinson disease. Hum. Mutat. 37, 292-300.
90. Gifford, J. L., Walsh, M. P. and Vogel, H. J. (2007). Structures and metal-ion-binding properties of the Ca2+-binding helix-loop-helix EF-hand motifs. Biochem. J. 405, 199-221.
91. Gitler, A. D., Chesi, A., Geddie, M. L., Strathearn, K. E., Hamamichi, S., Hill, K. J., Caldwell, K. A., Caldwell, G. A., Cooper, A. A., Rochet, J.-C. et al. (2009). Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat. Genet. 41, 308-315.
92. Glancy, B. and Balaban, R. S. (2012). Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51, 2959-2973.
93. Goldberg, J. A., Guzman, J. N., Estep, C. M., Ilijic, E., Kondapalli, J., Sanchez-Padilla, J. and Surmeier, D. J. (2012). Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease. Nat. Neurosci. 15, 1414-1421.
94. Goldman, S. M. (2014). Environmental toxins and Parkinson's disease. Annu. Rev. Pharmacol. Toxicol. 54, 141-164.
95. Gomez-Sanchez, R., Gegg, M. E., Bravo-San Pedro, J. M., Niso-Santano, M., Alvarez-Erviti, L., Pizarro-Estrella, E., Gutierrez-Martin, Y., Alvarez-Barrientos, A., Fuentes, J. M., Gonzalez-Polo, R. A. et al. (2014). Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression. Neurobiol. Dis. 62, 426-440.
96. Gomez-Suaga, P. and Hilfiker, S. (2012). LRRK2 as a modulator of lysosomal calcium homeostasis with downstream effects on autophagy. Autophagy 8, 692-693.
97. Gomez-Suaga, P., Churchill, G. C., Patel, S. and Hilfiker, S. (2012). A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium signalling. Biochem. Soc. Trans. 40, 1140-1146.
98. Gosavi, N., Lee, H.-J., Lee, J. S., Patel, S. and Lee, S.-J. (2002). Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion. J. Biol. Chem. 277, 48984-48992.
99. Grabarek, Z. (2011). Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins. Biochim. Biophys. Acta 1813, 913-921.
100. Guardia-Laguarta, C., Area-Gomez, E., Rub, C., Liu, Y., Magrane, J., Becker, D., Voos, W., Schon, E. A. and Przedborski, S. (2014). alpha-Synuclein is localized to mitochondria-associated ER membranes. J. Neurosci. 34, 249-259.
101. Guse, A. H. and Lee, H. C. (2008). NAADP: a universal Ca2+ trigger. Sci. Signal. 1, re10.
102. Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T. and Surmeier, D. J. (2010). Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468, 696-700.
103. Hashimoto, R., Nakamura, Y., Komai, S., Kashiwagi, Y., Tamura, K., Goto, T., Aimoto, S., Kaibuchi, K., Shiosaka, S. and Takeda, M. (2000). Site-specific phosphorylationof neurofilament-Lismediated bycalcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation. J. Neurochem. 75, 373-382.
104. Hatzifilippou, E., Koutsouraki, E., Banaki, T., Traka, M., Costa, V. G. and Baloyannis, S. J. (2008). Antibodies against GM1 in demented patients. Am. J. Alzheimers Dis. Other Demen. 23, 274-279.
105. Heeman, B., Van den Haute, C., Aelvoet, S.-A., Valsecchi, F., Rodenburg, R. J., Reumers, V., Debyser, Z., Callewaert, G., Koopman, W.J. H., Willems, P. H. G. M. et al. (2011). Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J. Cell Sci. 124, 1115-1125.
106. Hockey, L. N., Kilpatrick, B. S., Eden, E. R., Lin-Moshier, Y., Brailoiu, G. C., Brailoiu, E., Futter, C. E., Schapira, A. H., Marchant, J. S. and Patel, S. (2015). Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition. J. Cell Sci. 128, 232-238.
107. Hoglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L.-S., Klei, L., Rademakers, R., de Silva, R., Litvan, I., Riley, D. E. et al. (2011). Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699-705.
108. Hoover, C. M., Edwards, S. L., Yu, S.-C., Kittelmann, M., Richmond, J.E., Eimer, S., Yorks, R. M. and Miller, K. G. (2014). A novel CaM kinase II pathway controls the location of neuropeptide release from Caenorhabditis elegans motor neurons. Genetics 196, 745-765.
109. Hoozemans, J. J. M., van Haastert, E. S., Eikelenboom, P., de Vos, R. A. I., Rozemuller, J. M. and Scheper, W. (2007). Activation of the unfolded protein response in Parkinson's disease. Biochem. Biophys. Res. Commun. 354, 707-711.
110. Hu, Q. and Wang, G. (2016). Mitochondrial dysfunction in Parkinson's disease. Transl. Neurodegener. 5, 14.
111. Huang, Z., Ren, S., Jiang, Y. and Wang, T. (2016). PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila. Cell Death Dis. 7, e2179.
112. Hudmon, A. and Schulman, H. (2002). Neuronal Ca2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Annu. Rev. Biochem. 71, 473-510.
113. Hurley, M. J. and Dexter, D. T. (2012). Voltage-gated calcium channels and Parkinson's disease. Pharmacol. Ther. 133, 324-333.
114. Hurley, M. J., Brandon, B., Gentleman, S. M. and Dexter, D. T. (2013). Parkinson's disease is associated with altered expression of CaV1 channels and calcium-binding proteins. Brain 136, 2077-2097.
115. Hwang, O., Choi, H.J. and Park, S.Y. (1999).Up-regulation ofGTP cyclohydrolase I and tetrahydrobiopterin by calcium influx. Neuroreport 10, 3611-3614.
116. Ilijic, E., Guzman, J. N. and Surmeier, D. J. (2011). The L-type channel antagonist isradipine is neuroprotectivein a mouse model of Parkinson's disease. Neurobiol. Dis. 43, 364-371.
117. Iwatsubo, T., Nakano, I., Fukunaga, K.and Miyamoto, E. (1991). Ca2+/calmodulin-dependent protein kinaseIIimmunoreactivityinLewybodies.Acta Neuropathol.82, 159-163.
118. Jansen, E. J. R. and Martens, G. J. M. (2012). Novel insights into V-ATPase functioning: distinct roles for its accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. Curr. Protein Pept. Sci. 13, 124-133.
119. Jensen, M. B., Bhatia, V. K., Jao, C. C., Rasmussen, J. E., Pedersen, S. L., Jensen, K. J., Langen, R. and Stamou, D. (2011). Membrane curvature sensing by amphipathic helices: a single liposome study using alpha-synuclein and annexin B12. J. Biol. Chem. 286, 42603-42614.
120. Jiang, Y., Cong, P., Williams, S. R., Zhang, W., Na, T., Ma, H.-P. and Peng, J.-B. (2008). WNK4 regulates the secretory pathway via which TRPV5istargeted to the plasma membrane. Biochem. Biophys. Res. Commun. 375, 225-229.
121. Jin, J., Li, G. J., Davis, J., Zhu, D., Wang, Y., Pan, C. and Zhang, J. (2007). Identification of novel proteins associated with both alpha-synuclein and DJ-1. Mol. Cell. Proteomics 6, 845-859.
122. Johenning, F. W., Wenk, M. R., Uhlen, P., Degray, B., Lee, E., De Camilli, P. and Ehrlich, B. E. (2004). InsP3-mediated intracellular calcium signalling is altered by expression of synaptojanin-1. Biochem. J. 382, 687-694.
123. Johnson, G. V. W. and Foley, V. G. (1993). Calpain-mediated proteolysis of microtubule-associated protein 2 (MAP-2) is inhibited by phosphorylation by cAMP-dependent protein kinase, but not by Ca2+/calmodulin-dependent protein kinase II. J. Neurosci. Res. 34, 642-647.
124. Julien, J.-P. and Mushynski, W. E. (1998). Neurofilaments in health and disease. Prog. Nucleic Acid Res. Mol. Biol. 61, 1-23.
125. Kawasaki, H., Nakayama, S. and Kretsinger, R. H. (1998). Classification and evolution of EF-hand proteins. Biometals 11, 277-295.
126. Kayala, K. M. N., Dickinson, G. D., Minassian, A., Walls, K. C., Green, K. N. and LaFerla, F. M. (2012). Presenilin-null cells have altered two-pore calcium channel expression and lysosomal calcium: implications for lysosomal function. Brain Res. 1489, 8-16.
127. Khaliq, Z. M. and Bean, B. P. (2010). Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances. J. Neurosci. 30, 7401-7413.
128. Kieburtz, K., Tilley, B. C., Elm, J. J., Babcock, D., Hauser, R., Ross, G. W., Augustine, A. H., Augustine, E. U., Aminoff, M. J., Bodis-Wollner, I. G. et al. (2015). Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA 313, 584-593.
129. Kikuchi, A., Takeda, A., Kimpara, T., Nakagawa, M., Kawashima, R., Sugiura, M., Kinomura, S., Fukuda, H., Chida, K., Okita, N. et al. (2001). Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson's disease. J. Neurol. Sci. 193, 29-36.
130. Kilpatrick, B. S., Eden, E. R., Schapira, A. H., Futter, C. E. and Patel, S. (2013). Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals. J. Cell Sci. 126, 60-66.
131. Kilpatrick, B. S., Magalhaes, J., Beavan, M. S., McNeill, A., Gegg, M. E., Cleeter, M. W. J., Bloor-Young, D., Churchill, G. C., Duchen, M. R., Schapira, A. H. et al. (2016). Endoplasmic reticulum and lysosomal Ca(2)(+) stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts. Cell Calcium 59, 12-20.
132. Kim, C. H., Kim, J. H., Lee, J., Hsu, C. Y. and Ahn, Y. S. (2003). Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB. Biol. Chem. 384, 143-150.
133. Klionsky, D. J., Codogno, P., Cuervo, A. M., Deretic, V., Elazar, Z., Fueyo-Margareto, J., Gewirtz, D. A., Kroemer, G., Levine, B., Mizushima, N. et al. (2010). A comprehensive glossary of autophagy-related molecules and processes. Autophagy 6, 438-448.
134. Ko, J., Humbert, S., Bronson, R. T., Takahashi, S., Kulkarni, A. B., Li, E. and Tsai, L. H. (2001). p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J. Neurosci. 21, 6758-6771.
135. Korvatska, O., Strand, N. S., Berndt, J. D., Strovas, T., Chen, D.-H., Leverenz, J. B., Kiianitsa, K., Mata, I. F., Karakoc, E., Greenup, J. L. et al. (2013). Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). Hum. Mol. Genet. 22, 3259-3268.
136. Koschak, A., Reimer, D., Huber, I., Grabner, M., Glossmann, H., Engel, J. and Striessnig, J. (2001). alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J. Biol. Chem. 276, 22100-22106.
137. Krebs, C. E., Karkheiran, S., Powell, J. C., Cao, M., Makarov, V., Darvish, H., Di Paolo, G., Walker, R. H., Shahidi, G. A., Buxbaum, J. D. et al. (2013). The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures. Hum. Mutat. 34, 1200-1207.
138. Kretsinger, R. H. and Nockolds, C. E. (1973). Carp muscle calcium-binding protein. II. Structure determination and general description. J. Biol. Chem. 248, 3313-3326.
139. Krols, M., Bultynck, G. and Janssens, S. (2016). ER-Mitochondria contact sites: a new regulator of cellular calcium flux comes into play. J. Cell Biol. 214, 367-370.
140. Kumar, K. R., Djarmati-Westenberger, A. and Grunewald, A. (2011). Genetics of Parkinson's disease. Semin. Neurol. 31, 433-440.
141. Lanoue, A. C., Blatt, G. J. and Soghomonian, J.-J. (2013). Decreased parvalbumin mRNA expression in dorsolateral prefrontal cortex in Parkinson's disease. Brain Res. 1531, 37-47.
142. Lavoie, B. and Parent, A. (1991). Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. Neuroreport 2, 601-604.
143. Ledeen, R. W. and Wu, G. (2015). The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem. Sci. 40, 407-418.
144. Lee, C. H., Della, N. G., Chew, C. E. and Zack, D. J. (1996). Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of ras proteins. J. Neurosci. 16, 6784-6794.
145. Lee, D., Lee, S.-Y., Lee, E.-N., Chang, C.-S. and Paik, S. R. (2002). alpha-Synuclein exhibits competitive interaction between calmodulin and synthetic membranes. J. Neurochem. 82, 1007-1017.
146. Lee, S. Y., Wenk, M. R., Kim, Y., Nairn, A. C. and De Camilli, P. (2004). Regulation of synaptojanin1 bycyclin-dependent kinase 5atsynapses. Proc. Natl. Acad. Sci. USA 101, 546-551.
147. Lee, Y.-C., Lin, C.-H., Wu, R.-M., Lin, J.-W., Chang, C.-H. and Lai, M.-S. (2014). Antihypertensive agents and risk of Parkinson's disease: a nationwide cohort study. PLoS ONE 9, e98961.
148. Lee, J.-H., McBrayer, M. K., Wolfe, D. M., Haslett, L. J., Kumar, A., Sato, Y., Lie, P. P. Y., Mohan, P., Coffey, E. E., Kompella, U. et al. (2015). Presenilin 1 maintains lysosomal Ca(2+) homeostasis via TRPML1 by regulating vATPase-mediated lysosome acidification. Cell Rep. 12, 1430-1444.
149. Lees, A. J., Hardy, J. and Revesz, T. (2009). Parkinson's disease. Lancet 373, 2055-2066.
150. Lehmann, I. T., Bobrovskaya, L., Gordon, S. L., Dunkley, P. R. and Dickson, P. W. (2006). Differential regulation of the human tyrosine hydroxylase isoforms via hierarchical phosphorylation. J. Biol. Chem. 281, 17644-17651.
151. Lemasters, J. J., Theruvath, T. P., Zhong, Z. and Nieminen, A.-L. (2009). Mitochondrial calcium and the permeability transition in cell death. Biochim. Biophys. Acta 1787, 1395-1401.
152. Lesage, S., Bras, J., Cormier-Dequaire, F., Condroyer, C., Nicolas, A., Darwent, L., Guerreiro, R., Majounie, E., Federoff, M., Heutink, P. et al. (2015). Loss-of-function mutations in RAB39B are associated with typical early-onset Parkinson disease. Neurol Genet. 1, e9.
153. Lewit-Bentley, A. and Rety, S. (2000). EF-hand calcium-binding proteins. Curr. Opin. Struct. Biol. 10, 637-643.
154. Lin, M. K. and Farrer, M. J. (2014). Genetics and genomics of Parkinson's disease. Genome Med. 6, 48.
155. Lin, X., Parisiadou, L., Sgobio, C., Liu, G., Yu, J., Sun, L., Shim, H., Gu, X.-L., Luo, J., Long, C.-X. et al. (2012). Conditional expression of Parkinson's disease-related mutant alpha-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1. J. Neurosci. 32, 9248-9264.
156. Lindholm, D., Wootz, H. and Korhonen, L. (2006). ER stress and neurodegenerative diseases. Cell Death Differ. 13, 385-392.
157. Lipscombe, D., Helton, T. D. and Xu, W. (2004). L-type calcium channels: the low down. J. Neurophysiol. 92, 2633-2641.
158. Lloyd-Evans, E., Morgan, A. J., He, X., Smith, D. A., Elliot-Smith, E., Sillence, D. J., Churchill, G. C., Schuchman, E. H., Galione, A. and Platt, F. M. (2008). Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat. Med. 14, 1247-1255.
159. Luo, J., Sun, L., Lin, X., Liu, G., Yu, J., Parisiadou, L., Xie, C., Ding, J. and Cai, H. (2014). A calcineurin-and NFAT-dependent pathway is involved in alpha-synuclein-induced degeneration of midbrain dopaminergic neurons. Hum. Mol. Genet. 23, 6567-6574.
160. Luzio, J. P., Rous, B. A., Bright, N. A., Pryor, P. R., Mullock, B. M. and Piper, R. C. (2000). Lysosome-endosome fusion and lysosome biogenesis. J. Cell Sci. 113, 1515-1524.
161. Luzio, J.P., Bright, N. A. and Pryor, P.R.(2007). The roleofcalcium and other ions in sorting and delivery in the late endocytic pathway. Biochem. Soc. Trans. 35, 1088-1091.
162. Lynch-Day, M. A., Mao, K., Wang, K., Zhao, M. and Klionsky, D. J. (2012). The role of autophagy in Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a009357.
163. Marambaud, P., Dreses-Werringloer, U. and Vingtdeux, V. (2009). Calcium signaling in neurodegeneration. Mol. Neurodegener. 4, 20.
164. Marchi, S., Patergnani, S. and Pinton, P. (2014). The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. Biochim. Biophys. Acta 1837, 461-469.
165. Marras, C. and Tanner, C. M. (2004). Epidemiology of Parkinson's Disease. New York, NY: McGraw Hill.
166. Marti, M. J., Tolosa, E. and Campdelacreu, J. (2003). Clinical overview of the synucleinopathies. Mov. Disord. 18 Suppl. 6, 21-27.
167. Martin, I., Dawson, V. L. and Dawson, T. M. (2011). Recent advances in the genetics ofParkinson's disease. Annu. Rev. Genomics Hum. Genet. 12, 301-325.
168. Martin, Z. S., Neugebauer, V., Dineley, K. T., Kayed, R., Zhang, W., Reese, L. C. and Taglialatela, G. (2012). alpha-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases. J. Neurochem. 120, 440-452.
169. Martinez, J., Moeller, I., Erdjument-Bromage, H., Tempst, P. and Lauring, B. (2003). Parkinson's disease-associated alpha-synuclein is a calmodulin substrate. J. Biol. Chem. 278, 17379-17387.
170. Matsui, H., Sato, F., Sato, S., Koike, M., Taruno, Y., Saiki, S., Funayama, M., Ito, H., Taniguchi, Y., Uemura, N. et al. (2013). ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons. FEBS Lett. 587, 1316-1325.
171. McBrayer, M. K. and Nixon, R. A. (2013). Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime. Biochem. Soc. Trans. 41, 1495-1502.
172. McCormack, J. G. and Denton, R. M. (1990). The role of mitochondrial Ca2+ transport and matrix Ca2+ in signal transduction in mammalian tissues. Biochim. Biophys. Acta 1018, 287-291.
173. McKee, A. C., Kosik, K. S., Kennedy, M. B. and Kowall, N. W. (1990). Hippocampal neurons predisposed to neurofibrillary tangle formation are enriched in type II calcium/calmodulin-dependent protein kinase. J. Neuropathol. Exp. Neurol. 49, 49-63.
174. Meador, W.E., Means, A.R.and Quiocho, F.A.(1992). Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex. Science 257, 1251-1255.
175. Meador, W. E., Means, A. R. and Quiocho, F. A. (1993). Modulation of calmodulin plasticity in molecular recognition on the basis of X-ray structures. Science 262, 1718-1721.
176. Mehta, Z. B., Fine, N., Pullen, T. J., Cane, M. C., Hu, M., Chabosseau, P., Meur, G., Velayos-Baeza, A., Monaco, A. P., Marselli, L. et al. (2016). Changes in the expression of the type 2 diabetes-associated gene VPS13C in the beta-cell are associated with glucose intolerance in humans and mice. Am. J. Physiol. Endocrinol. Metab. 311, E488-E507.
177. Mercado, G., Castillo, V., Vidal, R. and Hetz, C. (2015). ER proteostasis disturbances in Parkinson's disease: novel insights. Front. Aging Neurosci. 7, 39.
178. Michael, D. J., Cai, H., Xiong, W., Ouyang, J. and Chow, R. H. (2006). Mechanisms of peptide hormone secretion. Trends Endocrinol. Metab. 17, 408-415.
179. Mignogna, M. L., Giannandrea, M., Gurgone, A., Fanelli, F., Raimondi, F., Mapelli, L., Bassani, S., Fang, H., Van Anken, E., Alessio, M. et al. (2015). The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition. Nat. Commun. 6, 6504.
180. Milovanovic, D., Platen, M., Junius, M., Diederichsen, U., Schaap, I. A. T., Honigmann, A., Jahn, R. and van den Bogaart, G. (2016). Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4, 5-Bisphosphate. J. Biol. Chem. 291, 7868-7876.
181. Mishima, T., Fujiwara, T., Sanada, M., Kofuji, T., Kanai-Azuma, M. and Akagawa, K. (2014). Syntaxin 1B, but not Syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses. PLoS ONE 9, e90004.
182. Mizuta, I., Tsunoda, T., Satake, W., Nakabayashi, Y., Watanabe, M., Takeda, A., Hasegawa, K., Nakashima, K., Yamamoto, M., Hattori, N. et al. (2008). Calbindin 1, fibroblast growth factor 20, and alpha-synuclein in sporadic Parkinson's disease. Hum. Genet. 124, 89-94.
183. Mosharov, E.V., Larsen, K.E., Kanter, E., Phillips, K.A., Wilson, K., Schmitz, Y., Krantz, D. E., Kobayashi, K., Edwards, R. H. and Sulzer, D. (2009). Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron 62, 218-229.
184. Mouatt-Prigent, A., Agid, Y. and Hirsch, E. C. (1994). Does the calcium binding protein calretinin protect dopaminergic neurons against degeneration in Parkinson's disease? Brain Res. 668, 62-70.
185. Mouatt-Prigent, A., Karlsson, J.-O., Yelnik, J., Agid, Y. and Hirsch, E. C. (2000). Calpastatin immunoreactivity in the monkey and human brain of control subjects and patients with Parkinson's disease. J. Comp. Neurol. 419, 175-192.
186. Moussaud, S., Jones, D. R., Moussaud-Lamodiere, E. L., Delenclos, M., Ross, O. A. and McLean, P. J. (2014). Alpha-synuclein and tau: teammates in neurodegeneration? Mol. Neurodegener. 9, 43.
187. Mu, T.-W., Fowler, D. M. and Kelly, J. W. (2008). Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis. PLoS Biol. 6, e26.
188. Mukherjee, A., Morales-Scheihing, D., Gonzalez-Romero, D., Green, K., Taglialatela, G. and Soto, C. (2010). Calcineurin inhibition at the clinical phase of prion disease reduces neurodegeneration, improves behavioral alterations and increases animal survival. PLoS Pathog. 6, e1001138.
189. Muller, A., Kukley, M., Stausberg, P., Beck, H., Muller, W. and Dietrich, D. (2005). Endogenous Ca2+ buffer concentration and Ca2+ microdomains in hippocampal neurons. J. Neurosci. 25, 558-565.
190. Murata, K., Yoshino, Y., Tsuruma, K., Moriguchi, S., Oyagi, A., Tanaka, H., Ishisaka, M., Shimazawa, M., Fukunaga, K. and Hara, H. (2015). The extracellular fragment of GPNMB (Glycoprotein nonmelanosoma protein B, osteoactivin) improves memory and increases hippocampal GluA1 levels in mice. J. Neurochem. 132, 583-594.
191. Nalls, M. A., Pankratz, N., Lill, C. M., Do, C. B., Hernandez, D. G., Saad, M., DeStefano, A. L., Kara, E., Bras, J., Sharma, M. et al. (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat. Genet. 46, 989-993.
192. Nath, S., Goodwin, J., Engelborghs, Y. and Pountney, D. L. (2011). Raised calcium promotes alpha-synuclein aggregate formation. Mol. Cell. Neurosci. 46, 516-526.
193. Navaroli, D. M., Stevens, Z. H., Uzelac, Z., Gabriel, L., King, M. J., Lifshitz, L. M., Sitte, H. H. and Melikian, H. E. (2011). The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking. J. Neurosci. 31, 13758-13770.
194. Nayak, L. and De, R. K. (2007). An algorithm for modularization of MAPK and calcium signaling pathways: comparative analysis among different species. J. Biomed. Inform. 40, 726-749.
195. Nelson, O., Supnet, C., Tolia, A., Horre, K., De Strooper, B. and Bezprozvanny, I. (2011). Mutagenesis mapping of the Presenilin 1 calcium leak conductance pore. J. Biol. Chem. 286, 22339-22347.
196. Neuhoff, H., Neu, A., Liss, B.and Roeper, J.(2002). I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J. Neurosci. 22, 1290-1302.
197. Nishi, A., Bibb, J. A., Matsuyama, S., Hamada, M., Higashi, H., Nairn, A. C. and Greengard, P. (2002). Regulation of DARPP-32 dephosphorylation at PKA-and Cdk5-sites by NMDA and AMPA receptors: distinct rolesof calcineurin and protein phosphatase-2A. J. Neurochem. 81, 832-841.
198. Nixon, R. A. (2013). The role of autophagy in neurodegenerative disease. Nat. Med. 19, 983-997.
199. Nuber, S. and Selkoe, D. J. (2016). Caspase-1 clipping causes complications for alpha-synuclein. Proc. Natl. Acad. Sci. USA 113, 9958-9960.
200. Nuscher, B., Kamp, F., Mehnert, T., Odoy, S., Haass, C., Kahle, P. J. and Beyer, K. (2004). alpha-synuclein has a high affinity for packing defects in a bilayer membrane-a thermodynamics study. J. Biol. Chem. 279, 21966-21975.
201. Ohshima, T., Ward, J.M., Huh, C.G., Longenecker, G., Veeranna, G., Pant, H.C., Brady, R. O., Martin, L. J. and Kulkarni, A. B. (1996). Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc. Natl. Acad. Sci. USA 93, 11173-11178.
202. Olah, J., Vincze, O., Virok, D., Simon, D., Bozso, Z., Tokesi, N., Horvath, I., Hlavanda, E., Kovacs, J., Magyar, A. et al. (2011). Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J. Biol. Chem. 286, 34088-34100.
203. Olson, P. A., Tkatch, T., Hernandez-Lopez, S., Ulrich, S., Ilijic, E., Mugnaini, E., Zhang, H., Bezprozvanny, I. and Surmeier, D. J. (2005). G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J. Neurosci. 25, 1050-1062.
204. Omura, T., Kaneko, M., Okuma, Y., Matsubara, K. and Nomura, Y. (2013). Endoplasmic reticulum stress and Parkinson's disease: the role of HRD1 in averting apoptosis in neurodegenerative disease. Oxid. Med. Cell Longev. 2013, 239854.
205. Ortner, N. J. and Striessnig, J. (2016). L-type calcium channels as drug targets in CNS disorders. Channels 10, 7-13.
206. Oslowski, C. M., Zhou, Q., Schafer, C., Kirber, M. and Bolotina, V. (2013). New causal relationship between PLA2g6, store-operated Ca2+ entry, refilling of Ca2+ stores and ER stress in mouse embryonic fibroblasts. FASEBJ. 27 Suppl. 1198.2.
207. Ottolini, D., Cali, T., Negro, A. and Brini, M. (2013). The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum. Mol. Genet. 22, 2152-2168.
208. Palop, J. J., Jones, B., Kekonius, L., Chin, J., Yu, G.-Q., Raber, J., Masliah, E. and Mucke, L. (2003). Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc. Natl. Acad. Sci. USA 100, 9572-9577.
209. Pankratz, N., Beecham, G. W., DeStefano, A. L., Dawson, T. M., Doheny, K. F., Factor, S. A., Hamza, T. H., Hung, A. Y., Hyman, B. T., Ivinson, A. J. et al. (2012). Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2. Ann. Neurol. 71, 370-384.
210. Parekh, A. B. (2008). Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function. J. Physiol. 586, 3043-3054.
211. Park, J.-S., Mehta, P., Cooper, A. A., Veivers, D., Heimbach, A., Stiller, B., Kubisch, C., Fung, V. S., Krainc, D., Mackay-Sim, A. et al. (2011). Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism. Hum. Mutat. 32, 956-964.
212. Pasternak, B., Svanstrom, H., Nielsen, N. M., Fugger, L., Melbye, M. and Hviid, A. (2012). Use of calcium channel blockers and Parkinson's disease. Am. J. Epidemiol. 175, 627-635.
213. Patel, S. and Docampo, R. (2010). Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. Trends Cell Biol. 20, 277-286.
214. Patel, S. and Muallem, S. (2011). Acidic Ca(2+) stores come to the fore. Cell Calcium 50, 109-112.
215. Pathak, T., Agrawal, T., Richhariya, S., Sadaf, S. and Hasan, G. (2015). Store-operated calcium entry through orai is required for transcriptional maturation of the flight circuit in Drosophila. J. Neurosci. 35, 13784-13799.
216. Perier, C. and Vila, M. (2012). Mitochondrial biology and Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a009332.
217. Petersen, O. H., Michalak, M. and Verkhratsky, A. (2005). Calcium signalling: past, present and future. Cell Calcium 38, 161-169.
218. Phillips, M. J. and Voeltz, G. K. (2016). Structure and function of ER membrane contact sites with other organelles. Nat. Rev. Mol. Cell Biol. 17, 69-82.
219. Pickrell, A. M. and Youle, R. J. (2015). The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. Neuron 85, 257-273.
220. Pitt, S. J., Funnell, T. M., Sitsapesan, M., Venturi, E., Rietdorf, K., Ruas, M., Ganesan, A., Gosain, R., Churchill, G. C., Zhu, M. X. et al. (2010). TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. J. Biol. Chem. 285, 35039-35046.
221. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R. et al. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047.
222. Puopolo, M., Raviola, E. and Bean, B. P. (2007). Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J. Neurosci. 27, 645-656.
223. Qu, D., Rashidian, J., Mount, M. P., Aleyasin, H., Parsanejad, M., Lira, A., Haque, E., Zhang, Y., Callaghan, S., Daigle, M. et al. (2007). Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron 55, 37-52.
224. Ramirez, A., Heimbach, A., Grundemann, J., Stiller, B., Hampshire, D., Cid, L. P., Goebel, I., Mubaidin, A. F., Wriekat, A.-L., Roeper, J. et al. (2006). Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat. Genet. 38, 1184-1191.
225. Ramonet, D., Podhajska, A., Stafa, K., Sonnay, S., Trancikova, A., Tsika, E., Pletnikova, O., Troncoso, J. C., Glauser, L. and Moore, D. J. (2012). PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity. Hum. Mol. Genet. 21, 1725-1743.
226. Rcom-H'cheo-Gauthier, A. N., Davis, A., Meedeniya, A. C. B. and Pountney, D. L. (2016). Alpha-synuclein aggregates are excluded from calbindin-D28k-positive neurons in dementia with Lewy bodies and a unilateral rotenone mouse model. Mol. Cell. Neurosci. 77, 65-75.
227. Reese, L. C., Zhang, W. R., Dineley, K. T., Kayed, R. and Taglialatela, G. (2008). Selective induction of calcineurin activity and signaling by oligomeric amyloid beta. Aging Cell 7, 824-835.
228. Rendon, W. O., Martinez-Alonso, E., Tomas, M., Martinez-Martinez, N. and Martinez-Menarguez, J. A. (2013). Golgi fragmentation is Rab and SNARE dependent in cellular models of Parkinson's disease. Histochem. Cell Biol. 139, 671-684.
229. Ritz, B., Rhodes, S. L., Qian, L., Schernhammer, E., Olsen, J. H. and Friis, S. (2010). L-type calciumchannel blockers and Parkinson disease inDenmark. Ann. Neurol. 67, 600-606.
230. Rivero-Rios, P., Gomez-Suaga, P., Fdez, E. and Hilfiker, S. (2014). Upstream deregulation of calcium signaling in Parkinson's disease. Front. Mol. Neurosci. 7, 53.
231. Rizzuto, R. and Pozzan, T. (2006). Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol. Rev. 86, 369-408.
232. Rizzuto, R., Marchi, S., Bonora, M., Aguiari, P., Bononi, A., De Stefani, D., Giorgi, C., Leo, S., Rimessi, A., Siviero, R. et al. (2009). Ca(2+) transfer from the ER to mitochondria: when, how and why. Biochim. Biophys. Acta 1787, 1342-1351.
233. Rizzuto, R., DeStefani, D., Raffaello, A. and Mammucari, C. (2012). Mitochondria as sensors and regulators of calcium signalling. Nat. Rev. Mol. Cell Biol. 13, 566-578.
234. Rosales, J. L., Nodwell, M. J., Johnston, R. N. and Lee, K.-Y. (2000). Cdk5/p25 (nck5a) interaction with synaptic proteins in bovine brain. J. Cell. Biochem. 78, 151-159.
235. Rozkalne, A., Hyman, B. T. and Spires-Jones, T. L. (2011). Calcineurin inhibition with FK506 ameliorates dendritic spine density deficits in plaque-bearing Alzheimer model mice. Neurobiol. Dis. 41, 650-654.
236. Ryan, B. J., Hoek, S., Fon, E. A. and Wade-Martins, R. (2015). Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem. Sci. 40, 200-210.
237. Saad, M., Lesage, S., Saint-Pierre, A., Corvol, J.-C., Zelenika, D., Lambert, J.-C., Vidailhet, M., Mellick, G. D., Lohmann, E., Durif, F. et al. (2011). Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population. Hum. Mol. Genet. 20, 615-627.
238. Sakamoto, K., Karelina, K. and Obrietan, K. (2011). CREB: a multifaceted regulator of neuronal plasticity and protection. J. Neurochem. 116, 1-9.
239. Samantaray, S., Ray, S. K. and Banik, N. L. (2008). Calpain as a potential therapeutic target in Parkinson's disease. CNS Neurol. Disord. Drug Targets 7, 305-312.
240. Santoro, L., Breedveld, G.J., Manganelli, F., Iodice, R., Pisciotta, C., Nolano, M., Punzo, F., Quarantelli, M., Pappata, S., Di Fonzo, A. et al. (2011). Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability. Neurogenetics 12, 33-39.
241. Sasabe, J., Chiba, T., Yamada, M., Okamoto, K., Nishimoto, I., Matsuoka, M. and Aiso, S. (2007). D-Serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J. 26, 4149-4159.
242. Schapira, A. H. V. (2013). Calcium dysregulation in Parkinson's disease. Brain 136, 2015-2016.
243. Schapira, A. H. V., Olanow, C. W., Greenamyre, J. T. and Bezard, E. (2014). Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives. Lancet 384, 545-555.
244. Schneider, J. S. (1998). GM1 ganglioside in the treatment of Parkinson's disease. Ann. N. Y. Acad. Sci. 845, 363-373.
245. Schneider, J. S., Sendek, S., Daskalakis, C. and Cambi, F. (2010). GM1 ganglioside in Parkinson's disease: results of a five year open study. J. Neurol. Sci. 292, 45-51.
246. Schneider, J. S., Gollomp, S. M., Sendek, S., Colcher, A., Cambi, F. and Du, W. (2013). A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients. J. Neurol. Sci. 324, 140-148.
247. Schroder, B., Wrocklage, C., Pan, C., Jager, R., Kosters, B., Schafer, H., Elsasser, H.-P., Mann, M. and Hasilik, A. (2007). Integral and associated lysosomal membrane proteins. Traffic 8, 1676-1686.
248. Shen, X., Valencia, C. A., Szostak, J., Dong, B. and Liu, R. (2005). Scanning the human proteome for calmodulin-binding proteins. Proc. Natl. Acad. Sci. USA 102, 5969-5974.
249. Sheng, Z. H. and Cai, Q. (2012). Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat. Rev. Neurosci. 13, 77-93.
250. Shi, G.-X., Han, J. and Andres, D. A. (2005). Rin GTPase couples nerve growth factor signaling to p38 and b-Raf/ERK pathways to promote neuronal differentiation. J. Biol. Chem. 280, 37599-37609.
251. Shulman, J. M., De Jager, P. L. and Feany, M. B. (2011). Parkinson's disease: genetics and pathogenesis. Annu. Rev. Pathol. 6, 193-222.
252. Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A. et al. (2009). Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N. Engl. J. Med. 361, 1651-1661.
253. Simon-Sanchez, J., Schulte, C., Bras, J. M., Sharma, M., Gibbs, J. R., Berg, D., Paisan-Ruiz, C., Lichtner, P., Scholz, S. W., Hernandez, D. G. et al. (2009). Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 41, 1308-1312.
254. Simuni, T., and the Parkinson Study Group. (2013). Phase II safety, tolerability, and dose selection study of isradipine as a potential disease-modifying intervention in early Parkinson's disease (STEADY-PD). Mov. Disord. 28, 1823-1831.
255. Simuni, T., Kieburtz, K., Tilley, B. J., Elm, J., Ravina, B., Babcock, D., Emborg, M., Hauser, R., Kamp, C., Morgan, J. C. et al. (2015). Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol. 14, 795-803.
256. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R. et al. (2003). alpha-Synuclein locus triplication causes Parkinson's disease. Science 302, 841.
257. Smani, T., Zakharov, S. I., Csutora, P., Leno, E., Trepakova, E. S. and Bolotina, V. M. (2004). A novel mechanism for the store-operated calcium influx pathway. Nat. Cell Biol. 6, 113-120.
258. Smith, P. D., Crocker, S. J., Jackson-Lewis, V., Jordan-Sciutto, K. L., Hayley, S., Mount, M. P., O'Hare, M. J., Callaghan, S., Slack, R. S., Przedborski, S. et al. (2003). Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 100, 13650-13655.
259. Smith, P. D., Mount, M. P., Shree, R., Callaghan, S., Slack, R. S., Anisman, H., Vincent, I., Wang, X., Mao, Z. and Park, D. S. (2006). Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J. Neurosci. 26, 440-447.
260. Snow, B. J., Rolfe, F. L., Lockhart, M. M., Frampton, C. M., O'Sullivan, J. D., Fung, V., Smith, R.A.J., Murphy, M. P.and Taylor, K. M.(2010). Adouble-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov. Disord. 25, 1670-1674.
261. Soto-Ortolaza, A. I., Behrouz, B., Wider, C., Vilarino-Guell, C., Heckman, M. G., Aasly, J. O., Mark Gibson, J., Lynch, T., Jasinska-Myga, B., Krygowska-Wajs, A. et al. (2010). Calbindin-1 association and Parkinson's disease. Eur. J. Neurol. 17, 208-211.
262. Sousa, S. C., Maciel, E. N., Vercesi, A. E. and Castilho, R. F. (2003). Ca2+-induced oxidative stress in brain mitochondria treated with the respiratory chain inhibitor rotenone. FEBS Lett. 543, 179-183.
263. Steinmetz, M. O., Pluss, C., Christen, U., Wolpensinger, B., Lustig, A., Werner, E. R., Wachter, H., Engel, A., Aebi, U., Pfeilschifter, J. et al. (1998). Rat GTP cyclohydrolase I is a homodecameric protein complex containing high-affinity calcium-binding sites. J. Mol. Biol. 279, 189-199.
264. Striessnig, J., Koschak, A., Sinnegger-Brauns, M. J., Hetzenauer, A., Nguyen, N. K., Busquet, P., Pelster, G. and Singewald, N. (2006). Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem. Soc. Trans. 34, 903-909.
265. Sudhof, T. C. (2013). A molecular machine for neurotransmitter release: synaptotagmin and beyond. Nat. Med. 19, 1227-1231.
266. Surmeier, D. J. and Schumacker, P. T. (2013). Calcium, bioenergetics, and neuronal vulnerability in Parkinson's disease. J. Biol. Chem. 288, 10736-10741.
267. Surmeier, D. J., Guzman, J. N., Sanchez-Padilla, J. and Goldberg, J. A. (2010). The origins of oxidant stress in Parkinson's disease and therapeutic strategies. Antioxid Redox Signal. 14, 1289-1301.
268. Surmeier, D. J., Guzman, J. N., Sanchez, J. and Schumacker, P. T. (2012). Physiological phenotype and vulnerability in Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a009290.
269. Surmeier, D. J., Schumacker, P. T., Guzman, J. D., Ilijic, E., Yang, B. and Zampese, E. (2016). Calcium and Parkinson's disease. Biochem. Biophys. Res. Commun. 483, 1013-1019.
270. Svennerholm, L., Bostrom, K., Jungbjer, B. and Olsson, L. (1994). Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem. 63, 1802-1811.
271. Taghibiglou, C., Martin, H. G. S., Lai, T. W., Cho, T., Prasad, S., Kojic, L., Lu, J., Liu, Y., Lo, E., Zhang, S. et al. (2009). Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries. Nat. Med. 15, 1399-1406.
272. Takahashi, M., Iseki, E. and Kosaka, K. (2000). Cyclin-dependent kinase 5 (Cdk5) associated with Lewy bodies in diffuse Lewy body disease. Brain Res. 862, 253-256.
273. Tang, T.-S., Tu, H. P., Chan, E.Y. W., Maximov, A., Wang, Z.N., Wellington, C. L., Hayden, M. R. and Bezprozvanny, I. (2003). Huntingtin and Huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1, 4, 5) triphosphate receptor type 1. Neuron 39, 227-239.
274. Teive, H. A. G., Troiano, A. R., Germiniani, F. M. B. and Werneck, L. C. (2004). Flunarizine and cinnarizine-induced parkinsonism: a historical and clinical analysis. Parkinsonism Relat. Disord. 10, 243-245.
275. Thayer, D. A., Jan, Y. N. and Jan, L. Y. (2013). Increased neuronal activity fragments the Golgi complex. Proc. Natl. Acad. Sci. USA 110, 1482-1487.
276. Tolia, A. and De Strooper, B. (2009). Structure and function of gamma-secretase. Semin. Cell Dev. Biol. 20, 211-218.
277. Tomiyama, H., Yoshino, H., Ogaki, K., Li, L., Yamashita, C., Li, Y., Funayama, M., Sasaki, R., Kokubo, Y., Kuzuhara, S. et al. (2011). PLA2G6 variant in Parkinson's disease. J. Hum. Genet. 56, 401-403.
278. Tsujii, S., Ishisaka, M. and Hara, H. (2015). Modulation of endoplasmic reticulum stress in Parkinson's disease. Eur. J. Pharmacol. 765, 154-156.
279. Van Maele-Fabry, G., Hoet, P., Vilain, F. and Lison, D. (2012). Occupational exposure to pesticides and Parkinson's disease: a systematic review and meta-analysis of cohort studies. Environ. Int. 46, 30-43.
280. Vance, J. E. (2014). MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim. Biophys. Acta 1841, 595-609.
281. Vilarino-Guell, C., Rajput, A., Milnerwood, A. J., Shah, B., Szu-Tu, C., Trinh, J., Yu, I., Encarnacion, M., Munsie, L. N., Tapia, L. et al. (2014). DNAJC13 mutations in Parkinson disease. Hum. Mol. Genet. 23, 1794-1801.
282. von Poser, C., Ichtchenko, K., Shao, X., Rizo, J. and Sudhof, T. C. (1997). The evolutionary pressure to inactivate. A subclass of synaptotagmins with an amino acid substitution that abolishes Ca2+ binding. J. Biol. Chem. 272, 14314-14319.
283. Wang, Z.-W. (2008). Regulation ofsynaptic transmission by presynaptic CaMKII and BK channels. Mol. Neurobiol. 38, 153-166.
284. Wang, X.-J. and Xu, J.-X. (2005). Possible involvement of Ca2+ signaling in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Neurosci. Lett. 376, 127-132.
285. Wang, J.-Z., Grundke-Iqbal, I. and Iqbal, K. (2007). Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur. J. Neurosci. 25, 59-68.
286. Wang, J., Huo, K., Ma, L., Tang, L., Li, D., Huang, X., Yuan, Y., Li, C., Wang, W., Guan, W. et al. (2011). Toward an understanding of the protein interaction network of the human liver. Mol. Syst. Biol. 7, 536.
287. Wang, J. Z., Xia, Y. Y., Grundke-Iqbal, I. and Iqbal, K. (2013a). Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis. 33 Suppl. 1, S123-S139.
288. Wang, R., McGrath, B. C., Kopp, R. F., Roe, M. W., Tang, X., Chen, G. and Cavener, D. R. (2013b). Insulin secretion and Ca2+ dynamics in beta-cells are regulated by PERK (EIF2AK3) in concert with calcineurin. J. Biol. Chem. 288, 33824-33836.
289. Wang, J.-Y., Gong, M.-Y., Ye, Y.-L., Ye, J.-M., Lin, G.-L., Zhuang, Q.-Q., Zhang, X. and Zhu, J.-H. (2015). The RIT2 and STX1B polymorphisms are associated with Parkinson's disease. Parkinsonism Relat. Disord. 21, 300-302.
290. Wang, W., Wang, X., Fujioka, H., Hoppel, C., Whone, A. L., Caldwell, M. A., Cullen, P. J., Liu, J. and Zhu, X. (2016). Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat. Med. 22, 54-63.
291. Wei, Y., Han, C., Wang, Y., Wu, B., Su, T., Liu, Y. and He, R. (2015). Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII. Aging Cell 14, 754-763.
292. White, B. C., Sullivan, J. M., DeGracia, D. J., O'Neil, B. J., Neumar, R. W., Grossman, L. I., Rafols, J. A. and Krause, G. S. (2000). Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J. Neurol. Sci. 179, 1-33.
293. Wilson, C. J. and Callaway, J. C. (2000). Coupled oscillator model of the dopaminergic neuron of the substantia nigra. J. Neurophysiol. 83, 3084-3100.
294. Wissemann, W. T., Hill-Burns, E. M., Zabetian, C. P., Factor, S. A., Patsopoulos, N., Hoglund, B., Holcomb, C., Donahue, R. J., Thomson, G., Erlich, H. et al. (2013). Association of Parkinson disease with structural and regulatory variants in the HLA region. Am. J. Hum. Genet. 93, 984-993.
295. Wojda, U., Salinska, E. and Kuznicki, J. (2008). Calcium ions in neuronal degeneration. IUBMB Life 60, 575-590.
296. Wu, H.-E., Baumgardt, S. L., Fang, J., Paterson, M., Liu, Y., Du, J., Shi, Y., Qiao, S., Bosnjak, Z. J., Warltier, D. C. et al. (2016). Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy. Sci. Rep. 6, 27925.
297. Xiao, J., Perry, G., Troncoso, J. and Monteiro, M. J. (1996). alpha-calcium-calmodulin-dependent kinase II is associated with paired helical filaments of Alzheimer's disease. J. Neuropathol. Exp. Neurol. 55, 954-963.
298. Xilouri, M., Brekk, O. R. and Stefanis, L. (2016). Autophagy and alpha-synuclein: relevance to Parkinson's disease and related synucleopathies. Mov. Disord. 31, 178-192.
299. Xu, W. and Lipscombe, D. (2001). Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J. Neurosci. 21, 5944-5951.
300. Xu, B., Liu, W., Deng, Y., Yang, T. Y., Feng, S. and Xu, Z. F. (2015). Inhibition of calpain prevents manganese-induced cell injury and alpha-synuclein oligomerization in organotypic brain slice cultures. PLoS ONE 10, e0119205.
301. Yamamoto, H., Yamauchi, E., Taniguchi, H., Ono, T. and Miyamoto, E. (2002). Phosphorylation of microtubule-associated protein tau by Ca2+/calmodulin-dependent protein kinase II in its tubulin binding sites. Arch. Biochem. Biophys. 408, 255-262.
302. Yamauchi, T. and Fujisawa, H. (1983). Disassembly of microtubules by the action of calmodulin-dependent protein kinase (Kinase II) which occurs only in the brain tissues. Biochem. Biophys. Res. Commun. 110, 287-291.
303. Yamauchi, T. and Fujisawa, H. (1984). Calmodulin-dependent protein kinase (kinase II) which is involved in the activation of tryptophan 5-monooxygenase catalyzes phosphorylation of tubulin. Arch. Biochem. Biophys. 234, 89-96.
304. Yan, J., Almilaji, A., Schmid, E., Elvira, B., Shimshek, D. R., van der Putten, H., Wagner, C. A., Shumilina, E. and Lang, F. (2015). Leucine-rich repeat kinase 2-sensitive Na+/Ca2+ exchanger activity in dendritic cells. FASEB J. 29, 1701-1710.
305. Yuan, H.-H., Chen, R.-J., Zhu, Y.-H., Peng, C.-L. and Zhu, X.-R. (2013). The neuroprotective effect of overexpression of calbindin-D(28k) in an animal model of Parkinson's disease. Mol. Neurobiol. 47, 117-122.
306. Zamponi, G. W. (2016). Targeting voltage-gated calcium channels in neurological and psychiatric diseases. Nat. Rev. Drug Discov. 15, 19-34.
307. Zeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B. D., Miyakawa, T., Bear, M. F. and Tonegawa, S. (2001). Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. Cell 107, 617-629.
308. Zhang, Y., Nijbroek, G., Sullivan, M. L., McCracken, A. A., Watkins, S. C., Michaelis, S. and Brodsky, J. L. (2001). Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol. Biol. Cell 12, 1303-1314.
309. Zhang, L., Shimoji, M., Thomas, B., Moore, D.J., Yu, S.W., Marupudi, N.I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M. et al. (2005). Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum. Mol. Genet. 14, 2063-2073.
310. Zhang, L., Liu, W., Szumlinski, K. K. and Lew, J. (2012). p10, the N-terminal domain of p35, protects against CDK5/p25-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 109, 20041-20046.
311. Zhou, Q., Li, J., Wang, H., Yin, Y. and Zhou, J. (2011). Identification of nigral dopaminergic neuron-enriched genes in adult rats. Neurobiol. Aging 32, 313-326.
312. Zhou, Q., Yen, A., Rymarczyk, G., Asai, H., Trengrove, C., Aziz, N., Kirber, M. T., Mostoslavsky, G., Ikezu, T., Wolozin, B. et al. (2016). Impairment of PARK14-dependent Ca(2+) signalling is a novel determinant of Parkinson's disease. Nat. Commun. 7, 10332.
313. Zhu, S., McGrath, B. C., Bai, Y., Tang, X. and Cavener, D. R. (2016). PERK regulates Gq protein-coupled intracellular Ca2+ dynamics in primary cortical neurons. Mol. Brain 9, 87.