Calcium: Alpha-synuclein interactions in alpha-synucleinopathies

Frontiers in Neuroscience

Volumn 10, Issue DEC, 2016, Pages

  Rcom H'cheo Gauthier, Alexandre N ^a   Osborne, Samantha L ^a   Meedeniya, Adrian C B ^a   Pountney, Dean L ^a  

^a GRIFFITH UNIVERSITY   (Australia)

Author keywords

A Synuclein; Calcium; Dementia with Lewy bodies; Multiple system atrophy; Parkinson's disease

Indexed keywords

ALPHA SYNUCLEIN; CALBINDIN; CALCIUM; CALCIUM CHANNEL; VOLTAGE GATED CALCIUM CHANNEL;

CALCIUM BINDING; CALCIUM CELL LEVEL; CALCIUM CHANNELOPATHY; CELL CULTURE; CELL INCLUSION; CHANNEL GATING; CYTOPLASM; DEGENERATIVE DISEASE; DIFFUSE LEWY BODY DISEASE; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HUMAN; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PROCESSING; SHORT SURVEY; SHY DRAGER SYNDROME;

EID: 85009731523     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2016.00570     Document Type: Short Survey

References (91)

1. Acosta, S. A., Tajiri, N., de la Pena, I., Bastawrous, M., Sanberg, P. R., Kaneko, Y., et al. (2015). Alpha-synuclein as a pathological link between chronic traumatic brain injury and Parkinson's disease. J. Cell. Physiol. 230, 1024-1032. doi: 10.1002/jcp.24830
2. Andressen, C., Blümcke, I., and Celio, M. R. (1993). Calcium-binding proteins: selective markers of nerve cells. Cell Tissue Res. 271, 181-208. doi: 10.1007/BF00318606
3. Angelova, P. R., and Abramov, A. Y. (2016). Alpha-synuclein and beta-amyloid-different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration. Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2016.07.103. [Epub ahead of print].
4. Angelova, P. R., Ludtmann, M. H., Horrocks, M. H., Negoda, A., Cremades, N., Klenerman, D., et al. (2016). Ca2+ is a key factor in a-synuclein-induced neurotoxicity. J. Cell Sci. 129, 1792-1801. doi: 10.1242/jcs.180737
5. Babu, C. S., and Ramanathan, M. (2011). Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics. Int. J. Dev. Neurosci. 29, 93-105. doi: 10.1016/j.ijdevneu.2010.08.001
6. Bu, J., Sathyendra, V., Nagykery, N., and Geula, C. (2003). Age-related changes in calbindin-D28k, calretinin, and parvalbumin-immunoreactive neurons in the human cerebral cortex. Exp. Neurol. 182, 220-231. doi: 10.1016/S0014-4886(03)00094-3
7. Buttner, S., Faes, L., Reichelt, W. N., Broeskamp, F., Habernig, L., Benke, S., et al. (2013). The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca2+ levels to alpha-synuclein toxicity in Parkinson's disease models. Cell Death Differ. 20, 465-477. doi: 10.1038/cdd.2012.142
8. Cali, T., Ottolini, D., Negro, A., and Brini, M. (2012). alpha-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J. Biol. Chem. 287, 17914-17929. doi: 10.1074/jbc.M111.302794
9. Castro Mdel, R., Suarez, E., Kraiselburd, E., Isidro, A., Paz, J., Ferder, L., et al. (2012). Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys. Exp. Gerontol. 47, 29-37. doi: 10.1016/j.exger.2011.10.002
10. Catterall, W. A., Perez-Reyes, E., Snutch, T. P., and Striessnig, J. (2005). International union of pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev. 57, 411-425. doi: 10.1124/pr.57.4.5
11. Chan, C. S., Guzman, J. N., Ilijic, E., Mercer, J. N., Rick, C., Tkatch, T., et al. (2007). 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 447, 1081-1086. doi: 10.1038/nature05865
12. Chartier-Harlin, M. C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., et al. (2004). alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364, 1167-1169. doi: 10.1016/S0140-6736(04)17103-1
13. Chemin, J., Monteil, A., Perez-Reyes, E., Nargeot, J., and Lory, P. (2001). Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide. EMBO J. 20, 7033-7040. doi: 10.1093/emboj/20.24.7033
14. Clayton, D. F., and George, J. M. (1999). Synucleins in synaptic plasticity and neurodegenerative disorders. J. Neurosci. Res. 58, 120-129. doi: 10.1002/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO;2-E
15. Conway, K. A., Harper, J. D., and Lansbury, P. T. (1998). Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat. Med. 4, 1318-1320. doi: 10.1038/3311
16. Conway, K. A., Lee, S. J., Rochet, J. C., Ding, T. T., Williamson, R. E., and Lansbury, P. T. Jr. (2000). Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc. Natl. Acad. Sci. U.S.A. 97, 571-576. doi: 10.1073/pnas.97.2.571
17. Dalfo, E., and Ferrer, I. (2008). Early alpha-synuclein lipoxidation in neocortex in Lewy body diseases. Neurobiol. Aging 29, 408-417. doi: 10.1016/j.neurobiolaging.2006.10.022
18. Dalgarno, D., Klevit, R. E., Levine, B. A., and Williams, R. J. P. (1984). The calcium receptor and trigger. Trends Pharmacol. Sci. 5, 266-271. doi: 10.1016/0165-6147(84)90442-5
19. Davydova, D., Marini, C., King, C., Klueva, J., Bischof, F., Romorini, S., et al. (2014). Bassoon specifically controls presynaptic P/Q-type Ca(2+) channels via RIM-binding protein. Neuron 82, 181-194. doi: 10.1016/j.neuron.2014.02.012
20. DeWitt, D. C., and Rhoades, E. (2013). a-Synuclein can inhibit SNARE-mediated vesicle fusion through direct interactions with lipid bilayers. Biochemistry 52, 2385-2387. doi: 10.1021/bi400236
21. Dryanovski, D. I., Guzman, J. N., Xie, Z., Galteri, D. J., Volpicelli-Daley, L. A., Lee, V. M., et al. (2013). Calcium entry and alpha-synuclein inclusions elevate dendritic mitochondrial oxidant stress in dopaminergic neurons. J. Neurosci. 33, 10154-10164. doi: 10.1523/JNEUROSCI.5311-12.2013
22. Ducic, T., Carboni, E., Lai, B., Chen, S., Michalke, B., Lázaro, D. F., et al. (2015). Alpha-synuclein regulates neuronal levels of manganese and calcium. ACS Chem. Neurosci. 6, 1769-1779. doi: 10.1021/acschemneuro.5b00093
23. Duckles, S. P., Tsai, H., and Buchholz, J. N. (1996). Evidence for decline in intracellular calcium buffering in adrenergic nerves of aged rats. Life Sci. 58, 2029-2035. doi: 10.1016/0024-3205(96)00194-4
24. Eschbach, J., and Danzer, K. M. (2014). alpha-Synuclein in Parkinson's disease: pathogenic function and translation into animal models. Neurodegener. Dis. 14, 1-17. doi: 10.1159/000354615
25. 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. doi: 10.1007/s12640-012-9366-z
26. Gaspar, P., Ben Jelloun, N., and Febvret, A. (1994). Sparing of the dopaminergic neurons containing calbindin-D28k and of the dopaminergic mesocortical projections in weaver mutant mice. Neuroscience 61, 293-305. doi: 10.1016/0306-4522(94)90232-1
27. German, D. C., Manaye, K. F., Sonsalla, P. K., and Brooks, B. A. (1992). Midbrain dopaminergic cell loss in Parkinson's disease and MPTP-induced parkinsonism: sparing of calbindin-D28k-containing cells. Ann. N. Y. Acad. Sci. 648, 42-62. doi: 10.1111/j.1749-6632.1992.tb24523.x
28. Goedert, M., Spillantini, M. G., Del Tredici, K., and Braak, H. (2013). 100 years of Lewy pathology. Nat. Rev. Neurol. 9, 13-24. doi: 10.1038/nrneurol.2012.242
29. Goldberg, J. A., Guzman, J. N., Estep, C. M., Ilijic, E., Kondapalli, J., Sanchez-Padilla, J., et al. (2012). Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease. Nat. Neurosci. 15, 1414-1421. doi: 10.1038/nn.3209
30. Goodwin, J., Nath, S., Engelborghs, Y., and Pountney, D. L. (2013). Raised calcium and oxidative stress cooperatively promote alpha-synuclein aggregate formation. Neurochem. Int. 62, 703-711. doi: 10.1016/j.neuint.2012.11.004
31. Hashida, H., Goto, J., Zhao, N., Takahashi, N., Hirai, M., Kanazawa, I., et al. (1998). Cloning and mapping of ZNF231, a novel brain-specific gene encoding neuronal double zinc finger protein whose expression is enhanced in a neurodegenerative disorder, multiple system atrophy (MSA). Genomics 54, 50-58. doi: 10.1006/geno.1998.5516
32. Hashimoto, M., Hsu, L. J., Rockenstein, E., Takenouchi, T., Mallory, M., and Masliah, E. (2002). alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells. J. Biol. Chem. 277, 11465-11472. doi: 10.1074/jbc.M111428200
33. Heady, T. N., Gomora, J. C., Macdonald, T. L., and Perez-Reyes, E. (2001). Molecular pharmacology of T-type Ca2+ channels. Jpn. J. Pharmacol. 85, 339-350. doi: 10.1254/jjp.85.339
34. Hettiarachchi, N. T., Parker, A., Dallas, M. L., Pennington, K., Hung, C. C., Pearson, H. A., et al. (2009). alpha-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells. J. Neurochem. 111, 1192-1201. doi: 10.1111/j.1471-4159.2009.06411.x
35. Ibanez, P., Bonnet, A. M., Debarges, B., Lohmann, E., Tison, F., Pollak, P., et al. (2004). Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet 364, 1169-1171. doi: 10.1016/S0140-6736(04)17104-3
36. Ivanova, D., Dirks, A., Montenegro-Venegas, C., Schone, C., Altrock, W. D., Marini, C., et al. (2015). Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo. EMBO J. 34, 1056-1077. doi: 10.15252/embj.201488796
37. Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., de Silva, H. A., et al. (1995). The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron 14, 467-475. doi: 10.1016/0896-6273(95)90302-X
38. Kanda, S., Bishop, J. F., Eglitis, M. A., Yang, Y., and Mouradian, M. M. (2000). Enhanced vulnerability to oxidative stress by alpha-synuclein mutations and C-terminal truncation. Neuroscience 97, 279-284. doi: 10.1016/S0306-4522(00)00077-4
39. Kim, B. G., Shin, D. H., Jeon, G. S., Seo, J. H., Kim, Y. W., Jeon, B. S., et al. (2000). Relative sparing of calretinin containing neurons in the substantia nigra of 6-OHDA treated rat parkinsonian model. Brain Res. 855, 162-165. doi: 10.1016/S0006-8993(99)02374-4
40. Kim, T. Y., Yoshimoto, T., Aoyama, Y., Niimi, K., and Takahashi, E. (2016). Analysis of the protective effects of a neuronal Cav2.1 calcium channel in brain injury. Neuroscience 313, 110-121. doi: 10.1016/j.neuroscience.2015.11.035
41. Koch, Y., Helferich, A. M., Steinacker, P., Oeckl, P., Walther, P., Weishaupt, J. H., et al. (2016). Aggregated a-synuclein increases SOD1 oligomerization in a mouse model of amyotrophic lateral sclerosis. Am. J. Pathol. 186, 2152-2161. doi: 10.1016/j.ajpath.2016.04.008
42. Krishnan, S., Chi, E. Y., Wood, S. J., Kendrick, B. S., Li, C., Garzon-Rodriguez, W., et al. (2003). Oxidative dimer formation is the critical rate-limiting step for Parkinson's disease alpha-synuclein fibrillogenesis. Biochemistry 42, 829-837. doi: 10.1021/bi026528t
43. Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., et al. (1998). Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet. 18, 106-108. doi: 10.1038/ng0298-106
44. Kume, K., Kikukawa, M., Hanyu, H., Takata, Y., Umahara, T., Sakurai, H., et al. (2012). Telomere length shortening in patients with dementia with Lewy bodies. Eur. J. Neurol. 19, 905-910. doi: 10.1111/j.1468-1331.2011.03655.x
45. Lesage, S., Anheim, M., Letournel, F., Bousset, L., Honore, A., Rozas, N., et al. (2013). G51D alpha-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann. Neurol. 73, 459-471. doi: 10.1002/ana.23894
46. Lin, M. T., Cantuti-Castelvetri, I., Zheng, K., Jackson, K. E., Tan, Y. B., Arzberger, T., et al. (2012). Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease. Ann. Neurol. 71, 850-854. doi: 10.1002/ana.23568
47. Lowe, R., Pountney, D. L., Jensen, P. H., Gai, W. P., and Voelcker, N. H. (2004). Calcium(II) selectively induces alpha-synuclein annular oligomers via interaction with the C-terminal domain. Protein Sci. 13, 3245-3252. doi: 10.1110/ps.04879704
48. Luth, E. S., Stavrovskaya, I. G., Bartels, T., Kristal, B. S., and Selkoe, D. J. (2014). Soluble, prefibrillar a-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction. J. Biol. Chem. 289, 21490-21507. doi: 10.1074/jbc.m113.545749
49. Maroteaux, L., Campanelli, J. T., and Scheller, R. H. (1988). Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804-2815.
50. McAllum, E. J., and Finkelstein, D. I. (2016). Metals in Alzheimer's and Parkinson's disease: relevance to dementia with lewy bodies. J. Mol. Neurosci. 60, 279-288. doi: 10.1007/s12031-016-0809-5
51. Melachroinou, K., Xilouri, M., Emmanouilidou, E., Masgrau, R., Papazafiri, P., Stefanis, L., et al. (2013). Deregulation of calcium homeostasis mediates secreted alpha-synuclein-induced neurotoxicity. Neurobiol. Aging 34, 2853-2865. doi: 10.1016/j.neurobiolaging.2013.06.006
52. Michaelis, M. L., Bigelow, D. J., Schoneich, C., Williams, T. D., Ramonda, L., Yin, D., et al. (1996). Decreased plasma membrane calcium transport activity in aging brain. Life Sci. 59, 405-412. doi: 10.1016/0024-3205(96)00319-0
53. Mironov, S. L. (2015). a-Synuclein forms non-selective cation channels and stimulates ATP-sensitive potassium channels in hippocampal neurons. J. Physiol. 593(Pt 1), 145-159. doi: 10.1113/jphysiol.2014.280974
54. Narhi, L., Wood, S. J., Steavenson, S., Jiang, Y., Wu, G. M., Anafi, D., et al. (1999). Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. J. Biol. Chem. 274, 9843-9846. doi: 10.1074/jbc.274.14.9843
55. Nath, S., Goodwin, J., Engelborghs, Y., and Pountney, D. L. (2011). Raised calcium promotes alpha-synuclein aggregate formation. Mol. Cell. Neurosci. 46, 516-526. doi: 10.1016/j.mcn.2010.12.004
56. Nath, S., Meuvis, J., Hendrix, J., Carl, S. A., and Engelborghs, Y. (2010). Early aggregation steps in a-synuclein as measured by FCS and FRET: evidence for a contagious conformational change. Biophys. J. 98, 1302-1311. doi: 10.1016/j.bpj.2009.12.4290
57. Navarria, L., Zaltieri, M., Longhena, F., Spillantini, M. G., Missale, C., Spano, P., et al. (2015). Alpha-synuclein modulates NR2B-containing NMDA receptors and decreases their levels after rotenone exposure. Neurochem. Int. 85-86, 14-23. doi: 10.1016/j.neuint.2015.03.008
58. Nielsen, M. S., Vorum, H., Lindersson, E., and Jensen, P. H. (2001). Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization. J. Biol. Chem. 276, 22680-22684. doi: 10.1074/jbc.M101181200
59. Parihar, M. S., Parihar, A., Fujita, M., Hashimoto, M., and Ghafourifar, P. (2008). Mitochondrial association of alpha-synuclein causes oxidative stress. Cell. Mol. Life Sci. 65, 1272-1284. doi: 10.1007/s00018-008-7589-1
60. 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. doi: 10.1002/mds.25639
61. Pasanen, P., Myllykangas, L., Siitonen, M., Raunio, A., Kaakkola, S., Lyytinen, J., et al. (2014). A novel a-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology. Neurobiol. Aging 35, 2180.e1-e5. doi: 10.1016/j.neurobiolaging.2014.03.024
62. 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. doi: 10.1093/aje/kwr362
63. Perez-Pinzon, M. A., Yenari, M. A., Sun, G. H., Kunis, D. M., and Steinberg, G. K. (1997). SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits. J. Neurol. Sci. 153, 25-31. doi: 10.1016/S0022-510X(97)00196-2
64. Perfeito, R., Ribeiro, M., and Rego, A. C. (2016). Alpha-synuclein-induced oxidative stress correlates with altered superoxide dismutase and glutathione synthesis in human neuroblastoma SH-SY5Y cells. Arch Toxicol. doi: 10.1007/s00204-016-1788-6. [Epub ahead of print].
65. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., et al. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047. doi: 10.1126/science.276.5321.2045
66. Pottorf, W. J., Duckles, S. P., and Buchholz, J. N. (2000). SERCA function declines with age in adrenergic nerves from the superior cervical ganglion. J. Auton. Pharmacol. 20, 281-290. doi: 10.1046/j.1365-2680.2000.00194.x
67. Pountney, D. L., Voelcker, N. H., and Gai, W. P. (2005). Annular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Neurotox. Res. 7, 59-67. doi: 10.1007/BF03033776
68. Proukakis, C., Dudzik, C. G., Brier, T., MacKay, D. S., Cooper, J. M., Millhauser, G. L., et al. (2013). A novel a-synuclein missense mutation in Parkinson disease. Neurology 80, 1062-1064. doi: 10.1212/WNL.0b013e31828727ba
69. Quilty, M. C., King, A. E., Gai, W. P., Pountney, D. L., West, A. K., Vickers, J. C., et al. (2006). Alpha-synuclein is upregulated in neurones in response to chronic oxidative stress and is associated with neuroprotection. Exp. Neurol. 199, 249-256. doi: 10.1016/j.expneurol.2005.10.018
70. Radford, R., Wong, M. B., and Pountney, D. L. (2014). "Neurodegenerative aspects of multiple system atrophy," in Handbook of Neurotoxicity, ed R. M. Kostrzewa (New York, NY: Springer Science + Business Media), 2157-2180.
71. Rcom-H'cheo-Gauthier, A., Davis, A., Meedeniya, A., 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. doi: 10.1016/j.mcn.2016.10.003
72. Recasens, A., Dehay, B., Bove, J., Carballo-Carbajal, I., Dovero, S., Perez-Villalba, A., et al. (2014). Lewy body extracts from Parkinson disease brains trigger alpha-synuclein pathology and neurodegeneration in mice and monkeys. Ann. Neurol. 75, 351-362. doi: 10.1002/ana.24066
73. Reznichenko, L., Cheng, Q., Nizar, K., Gratiy, S. L., Saisan, P. A., Rockenstein, E. M., et al. (2012). In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy. J. Neurosci. 32, 9992-9998. doi: 10.1523/JNEUROSCI.1270-12.2012
74. Ritz, B., Rhodes, S. L., Qian, L., Schernhammer, E., Olsen, J. H., and Friis, S. (2010). L-type calcium channel blockers and Parkinson disease in Denmark. Ann. Neurol. 67, 600-606. doi: 10.1002/ana.21937
75. Rockenstein, E., Nuber, S., Overk, C. R., Ubhi, K., Mante, M., Patrick, C., et al. (2014). Accumulation of oligomer-prone alpha-synuclein exacerbates synaptic and neuronal degeneration in vivo. Brain 137(Pt 5), 1496-1513. doi: 10.1093/brain/awu057
76. Saito, Y., Miyasaka, T., Hatsuta, H., Takahashi-Niki, K., Hayashi, K., Mita, Y., et al. (2014). Immunostaining of oxidized DJ-1 in human and mouse brains. J. Neuropathol. Exp. Neurol. 73, 714-728. doi: 10.1097/NEN.0000000000000087
77. Santner, A., and Uversky, V. N. (2010). Metalloproteomics and metal toxicology of a-synuclein. Metallomics. 2, 378-392. doi: 10.1039/b926659c
78. Simms, B. A., and Zamponi, G. W. (2014). Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron 82, 24-45. doi: 10.1016/j.neuron.2014.03.016
79. Sims-Robinson, C., Hur, J., Hayes, J. M., Dauch, J. R., Keller, P. J., Brooks, S. V., et al. (2013). The role of oxidative stress in nervous system aging. PLoS ONE 8:e68011. doi: 10.1371/journal.pone.0068011
80. Singh, A., Verma, P., Balaji, G., Samantaray, S., and Mohanakumar, K. P. (2016). Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. Neurochem. Int. 99, 221-232. doi: 10.1016/j.neuint.2016.07.003
81. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., et al. (2003). a-Synuclein locus triplication causes Parkinson's disease. Science 302:841. doi: 10.1126/science.1090278
82. 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. doi: 10.1016/j.bbrc.2016.08.168. [Epub ahead of print].
83. Talley, E. M., Cribbs, L. L., Lee, J. H., Daud, A., Perez-Reyes, E., and Bayliss, D. A. (1999). Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J. Neurosci. 19, 1895-1911.
84. Toescu, E. C., and Verkhratsky, A. (2007). Role of calcium in normal aging and neurodegeneration. Aging Cell 6:265. doi: 10.1111/j.1474-9726.2007.00299.x
85. Tsuboi, K., Kimber, T. A., and Shults, C. W. (2000). Calretinin-containing axons and neurons are resistant to an intrastriatal 6-hydroxydopamine lesion. Brain Res. 866, 55-64. doi: 10.1016/S0006-8993(00)02219-8
86. Ubhi, K., Lee, P. H., Adame, A., Inglis, C., Mante, M., Rockenstein, E., et al. (2009). Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of alpha-synuclein in a transgenic mouse model of multiple system atrophy. J. Neurosci. Res. 87, 2728-2739. doi: 10.1002/jnr.22089
87. Wildburger, N. C., Lin-Ye, A., Baird, M. A., Lei, D., and Bao, J. (2009). Neuroprotective effects of blockers for T-type calcium channels. Mol. Neurodegener. 4:44. doi: 10.1186/1750-1326-4-44
88. Yamada, T., McGeer, P. L., Baimbridge, K. G., and McGeer, E. G. (1990). Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res. 526, 303-307.
89. Yunker, A. M., Sharp, A. H., Sundarraj, S., Ranganathan, V., Copeland, T. D., and McEnery, M. W. (2003). Immunological characterization of T-type voltage-dependent calcium channel CaV3.1 (alpha 1G) and CaV3.3 (alpha 1I) isoforms reveal differences in their localization, expression, and neural development. Neuroscience 117, 321-335. doi: 10.1016/S0306-4522(02)00936-3
90. Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., et al. (2004). The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164-173. doi: 10.1002/ana.10795
91. Zhou, Y., Yang, W., Kirberger, M., Lee, H. W., Ayalasomayajula, G., and Yang, J. J. (2006). Prediction of EF-hand calcium binding proteins and analysis of bacterial EF hand proteins. Proteins 65, 643-655. doi: 10.1002/prot.21139