Calcium dysregulation links ALS defective proteins and motor neuron selective vulnerability

Frontiers in Cellular Neuroscience

Volumn 9, Issue June, 2015, Pages 1-6

  Leal, Sónia S ^a,b   Gomes, Cláudio M ^a,b  

^a UNIVERSITY OF LISBON   (Portugal)

^b INSTITUTO DE TECNOLOGIA QUÍMICA E BIOLÓGICA   (Portugal)

Author keywords

ALS; Calcium homeostasis; Neurodegenerative diseases; Proteinopathies; SOD1

Indexed keywords

ATAXIN 2; CALBINDIN; CALCIUM BINDING PROTEIN; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CALPAIN; MATRILYSIN; NUCLEIC ACID BINDING PROTEIN; PARVALBUMIN; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; CLINICAL FEATURE; DISEASE PREDISPOSITION; GENE MUTATION; GENETIC HETEROGENEITY; HUMAN; MOTOR NEURODEGENERATION; MOTOR NEURON DISEASE; NERVE CELL PLASTICITY; OXIDATIVE STRESS; REGULATORY MECHANISM; RISK FACTOR; SIGNAL TRANSDUCTION;

EID: 84935841103     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2015.00225     Document Type: Article

References (85)

1. Aggad, D., Vérièpe, J., Tauffenberger, A., and Parker, J. A. (2014). TDP-43 toxicity proceeds via calcium dysregulation and necrosis in aging Caenorhabditis elegans motor neurons. J. Neurosci. 34, 12093-12103. doi: 10.1523/jneurosci.2495-13.2014
2. Al-Chalabi, A., Jones, A., Troakes, C., King, A., Al-Sarraj, S., and van den Berg, L. H. (2012). The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuropathol. 124, 339-352. doi: 10.1007/s00401-012-1022-4
3. Alexianu, M. E., Ho, B. K., Mohamed, A. H., La Bella, V., Smith, R. G., and Appel, S. H. (1994). The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis. Ann. Neurol. 36, 846-858. doi: 10.1002/ana.410360608
4. Ashpole, N. M., Song, W., Brustovetsky, T., Engleman, E. A., Brustovetsky, N., Cummins, T. R., et al. (2012). Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibition induces neurotoxicity via dysregulation of glutamate/calcium signaling and hyperexcitability. J. Biol. Chem. 287, 8495-8506. doi: 10.1074/jbc.m111.323915
5. Atkin, J. D., Farg, M. A., Soo, K. Y., Walker, A. K., Halloran, M., Turner, B. J., et al. (2014). Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis. J. Neurochem. 129, 190-204. doi: 10.1111/jnc.12493
6. Beers, D. R., Ho, B. K., Siklós, L., Alexianu, M. E., Mosier, D. R., Mohamed, A. H., et al. (2001). Parvalbumin overexpression alters immune-mediated increases in intracellular calcium and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis. J. Neurochem. 79, 499-509. doi: 10.1046/j.1471-4159.2001.00582.x
7. Bezprozvanny, I. B. (2010). Calcium signaling and neurodegeneration. Acta Naturae 2, 72-82
8. Blokhuis, A. M., Groen, E. J., Koppers, M., van den Berg, L. H., and Pasterkamp, R. J. (2013). Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol. 125, 777-794. doi: 10.1007/s00401-013-1125-6
9. Chen, Y. Z., Bennett, C. L., Huynh, H. M., Blair, I. P., Puls, I., Irobi, J., et al. (2004). DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am. J. Hum. Genet. 74, 1128-1135. doi: 10.1086/421054
10. Chen, X., Tang, T. S., Tu, H., Nelson, O., Pook, M., Hammer, R., et al. (2008). Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3. J. Neurosci. 28, 12713-12724. doi: 10.1523/JNEUROSCI.3909-08.2008
11. Convertini, P., Zhang, J., de la Grange, P., Hayward, L. J., Zhu, H., and Stamm, S. (2013). Genome wide array analysis indicates that an amyotrophic lateral sclerosis mutation of FUS causes an early increase of CAMK2N2 in vitro. Biochim. Biophys. Acta 1832, 1129-1135. doi: 10.1016/j.bbadis.2013.03.015
12. Cozzolino, M., and Carrì, M. T. (2012). Mitochondrial dysfunction in ALS. Prog. Neurobiol. 97, 54-66. doi: 10.1016/j.pneurobio.2011.06.003
13. DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256. doi: 10.1016/j.neuron.2011.09.011
14. Deng, H. X., Zhai, H., Bigio, E. H., Yan, J., Fecto, F., Ajroud, K., et al. (2010). FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann. Neurol. 67, 739-748. doi: 10.1002/ana.22051
15. De Vos, K. J., Mórotz, G. M., Stoica, R., Tudor, E. L., Lau, K. F., Ackerley, S., et al. (2012). VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Hum. Mol. Genet. 21, 1299-1311. doi: 10.1093/hmg/ddr559
16. Elden, A. C., Kim, H. J., Hart, M. P., Chen-Plotkin, A. S., Johnson, B. S., Fang, X., et al. (2010). Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466, 1069-1075. doi: 10.1038/nature09320
17. Estácio, S. G., Leal, S. S., Cristóvão, J. S., Faísca, P. F., and Gomes, C. M. (2015). Calcium binding to gatekeeper residues flanking aggregation-prone segments underlies non-fibrillar amyloid traits in superoxide dismutase 1 (SOD1). Biochim. Biophys. Acta 1854, 118-126. doi: 10.1016/j.bbapap.2014.11.005
18. Farg, M. A., Soo, K. Y., Warraich, S. T., Sundaramoorthy, V., Blair, I. P., and Atkin, J. D. (2013). Ataxin-2 interacts with FUS and intermediate-length polyglutamine expansions enhance FUS-related pathology in amyotrophic lateral sclerosis. Hum. Mol. Genet. 22, 717-728. doi: 10.1093/hmg/dds479
19. Forsberg, K., Jonsson, P. A., Andersen, P. M., Bergemalm, D., Graffmo, K. S., Hultdin, M., et al. (2010). Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients. PLoS One 5:e11552. doi: 10.1371/journal.pone.0011552
20. Grosskreutz, J., Van Den Bosch, L., and Keller, B. U. (2010). Calcium dysregulation in amyotrophic lateral sclerosis. Cell Calcium 47, 165-174. doi: 10.1016/j.ceca.2009.12.002
21. Guatteo, E., Carunchio, I., Pieri, M., Albo, F., Canu, N., Mercuri, N. B., et al. (2007). Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels’ activation in a genetic model of amyotrophic lateral sclerosis. Neurobiol. Dis. 28, 90-100. doi: 10.1016/j.nbd.2007.07.002
22. Hayashi, S., Amari, M., and Okamoto, K. (2013). Loss of calretinin- and parvalbumin-immunoreactive axons in anterolateral columns beyond the corticospinal tracts of amyotrophic lateral sclerosis spinal cords. J. Neurol. Sci. 331, 61-66. doi: 10.1016/j.jns.2013.05.008
23. Iguchi, Y., Katsuno, M., Ikenaka, K., Ishigaki, S., and Sobue, G. (2013). Amyotrophic lateral sclerosis: an update on recent genetic insights. J. Neurol. 260, 2917-2927. doi: 10.1007/s00415-013-7112-y
24. Jaarsma, D., Rognoni, F., van Duijn, W., Verspaget, H. W., Haasdijk, E. D., and Holstege, J. C. (2001). CuZn superoxide dismutase (SOD1) accumulates in vacuolated mitochondria in transgenic mice expressing amyotrophic lateral sclerosis-linked SOD1 mutations. Acta Neuropathol. 102, 293-305. doi: 10.1007/s004010100399
25. Jaiswal, M. K. (2013). Calcium, mitochondria and the pathogenesis of ALS: the good, the bad and the ugly. Front. Cell. Neurosci. 7:199. doi: 10.3389/fncel.2013.00199
26. Jaiswal, M. K., and Keller, B. U. (2009). Cu/Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of mitochondria and perturbs Ca2+ homeostasis in SOD1G93A mice. Mol. Pharmacol. 75, 478-489. doi: 10.1124/mol.108.050831
27. Johnson, J. O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V. M., Trojanowski, J. Q., et al. (2010). Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68, 857-864. doi: 10.1016/j.neuron.2010.11.036
28. Johnson, J. O., Pioro, E. P., Boehringer, A., Chia, R., Feit, H., Renton, A. E., et al. (2014). Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat. Neurosci. 17, 664-666. doi: 10.1038/nn.3688
29. Jung, C., Higgins, C. M., and Xu, Z. (2002). Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. J. Neurochem. 83, 535-545. doi: 10.1046/j.1471-4159.2002.01112.x
30. Kanekura, K., Hashimoto, Y., Niikura, T., Aiso, S., Matsuoka, M., and Nishimoto, I. (2004). Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through RhoGEF domain by interacting with SOD1 mutants. J. Biol. Chem. 279, 19247-19256. doi: 10.1074/jbc.m313236200
31. Kasumu, A., and Bezprozvanny, I. (2012). Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias. Cerebellum 11, 630-639. doi: 10.1007/s12311-010-0182-9
32. Kawamata, H., and Manfredi, G. (2010). Mitochondrial dysfunction and intracellular calcium dysregulation in ALS. Mech. Ageing Dev. 131, 517-526. doi: 10.1016/j.mad.2010.05.003
33. Kim, M. J., Jo, D. G., Hong, G. S., Kim, B. J., Lai, M., Cho, D. H., et al. (2002). Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death. Proc. Natl. Acad. Sci. U S A 99, 9870-9875. doi: 10.1073/pnas.152336999
34. Kim, S., Leal, S. S., Ben Halevy, D., Gomes, C. M., and Lev, S. (2010). Structural requirements for VAP-B oligomerization and their implication in amyotrophic lateral sclerosis-associated VAP-B(P56S) neurotoxicity. J. Biol. Chem. 285, 13839-13849. doi: 10.1074/jbc.m109.097345
35. Kruman, I. I., Pedersen, W. A., Springer, J. E., and Mattson, M. P. (1999). ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp. Neurol. 160, 28-39. doi: 10.1006/exnr.1999.7190
36. Lai, C., Xie, C., McCormack, S. G., Chiang, H. C., Michalak, M. K., Lin, X., et al. (2006). Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking. J. Neurosci. 26, 11798-11806. doi: 10.1523/jneurosci.2084-06.2006
37. Lautenschläger, J., Prell, T., Ruhmer, J., Weidemann, L., Witte, O. W., and Grosskreutz, J. (2013). Overexpression of human mutated G93A SOD1 changes dynamics of the ER mitochondria calcium cycle specifically in mouse embryonic motor neurons. Exp. Neurol. 247, 91-100. doi: 10.1016/j.expneurol.2013.03.027
38. Leal, S. S., Cardoso, I., Valentine, J. S., and Gomes, C. M. (2013). Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar amyloid: a link to toxic effects of calcium overload in amyotrophic lateral sclerosis (ALS)? J. Biol. Chem. 288, 25219-25228. doi: 10.1074/jbc.M113.470740
39. Liu, J., Lillo, C., Jonsson, P. A., Vande Velde, C., Ward, C. M., Miller, T. M., et al. (2004). Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43, 5-17. doi: 10.1016/j.neuron.2004.06.016
40. Liu, J., Tang, T. S., Tu, H., Nelson, O., Herndon, E., Huynh, D. P., et al. (2009). Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2. J. Neurosci. 29, 9148-9162. doi: 10.1523/JNEUROSCI.0660-09.2009
41. Maekawa, S., Leigh, P. N., King, A., Jones, E., Steele, J. C., Bodi, I., et al. (2009). TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations. Neuropathology 29, 672-683. doi: 10.1111/j.1440-1789.2009.01029.x
42. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., et al. (2010). Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465, 223-226. doi: 10.1038/nature08971
43. Masutani, T., Taguchi, K., Kumanogoh, H., Nakamura, S., and Maekawa, S. (2008). Molecular interaction of neurocalcin alpha with alsin (ALS2). Neurosci. Lett. 438, 26-28. doi: 10.1016/j.neulet.2008.04.066
44. Mattiazzi, M., D’Aurelio, M., Gajewski, C. D., Martushova, K., Kiaei, M., Beal, M. F., et al. (2002). Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J. Biol. Chem. 277, 29626-29633. doi: 10.1074/jbc.m203065200
45. Migheli, A., Cordera, S., Bendotti, C., Atzori, C., Piva, R., and Schiffer, D. (1999). S-100beta protein is upregulated in astrocytes and motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis. Neurosci. Lett. 261, 25-28. doi: 10.1016/s0304-3940(98)01001-5
46. Mórotz, G. M., De Vos, K. J., Vagnoni, A., Ackerley, S., Shaw, C. E., and Miller, C. C. (2012). Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria. Hum. Mol. Genet. 21, 1979-1988. doi: 10.1093/hmg/dds011
47. Nihei, Y., Ito, D., and Suzuki, N. (2012). Roles of ataxin-2 in pathological cascades mediated by TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS). J. Biol. Chem. 287, 41310-41323. doi: 10.1074/jbc.m112.398099
48. Nishimura, A. L., Mitne-Neto, M., Silva, H. C., Richieri-Costa, A., Middleton, S., Cascio, D., et al. (2004). A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet. 75, 822-831. doi: 10.1086/425287
49. Osaka, M., Ito, D., Yagi, T., Nihei, Y., and Suzuki, N. (2015). Evidence of a link between ubiquilin 2 and optineurin in amyotrophic lateral sclerosis. Hum. Mol. Genet. 24, 1617-1629. doi: 10.1093/hmg/ddu575
50. Palecek, J., Lips, M. B., and Keller, B. U. (1999). Calcium dynamics and buffering in motoneurones of the mouse spinal cord. J. Physiol. 520(Pt. 2), 485-502. doi: 10.1111/j.1469-7793.1999.00485.x
51. Parone, P. A., Da Cruz, S., Han, J. S., McAlonis-Downes, M., Vetto, A. P., Lee, S. K., et al. (2013). Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. J. Neurosci. 33, 4657-4671. doi: 10.1523/jneurosci.1119-12.2013
52. Pedrini, S., Sau, D., Guareschi, S., Bogush, M., Brown, R. H. Jr., Naniche, N., et al. (2010). ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2. Hum. Mol. Genet. 19, 2974-2986. doi: 10.1093/hmg/ddq202
53. Pokrishevsky, E., Grad, L. I., Yousefi, M., Wang, J., Mackenzie, I. R., and Cashman, N. R. (2012). Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS One 7:e35050. doi: 10.1371/journal.pone.0035050
54. Prell, T., Lautenschläger, J., and Grosskreutz, J. (2013). Calcium-dependent protein folding in amyotrophic lateral sclerosis. Cell Calcium 54, 132-143. doi: 10.1016/j.ceca.2013.05.007
55. Prosser, D. C., Tran, D., Gougeon, P. Y., Verly, C., and Ngsee, J. K. (2008). FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transport and VAPB-mediated ER aggregation. J. Cell. Sci. 121, 3052-3061. doi: 10.1242/jcs.028696
56. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62. doi: 10.1038/362059a0
57. Rowland, L. P., and Shneider, N. A. (2001). Amyotrophic lateral sclerosis. N. Engl. J. Med. 344, 1688-1700. doi: 10.1056/NEJM200105313442207
58. Shaw, P. J., and Eggett, C. J. (2000). Molecular factors underlying selective vulnerability of motor neurons to neurodegeneration in amyotrophic lateral sclerosis. J. Neurol. 247(Suppl. 1), I17-I27. doi: 10.1007/bf03161151
59. Siklós, L., Engelhardt, J. I., Alexianu, M. E., Gurney, M. E., Siddique, T., and Appel, S. H. (1998). Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice. J. Neuropathol. Exp. Neurol. 57, 571-587. doi: 10.1097/00005072-199806000-00005
60. Siklós, L., Engelhardt, J., Harati, Y., Smith, R. G., Joó, F., and Appel, S. H. (1996). Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. Ann. Neurol. 39, 203-216. doi: 10.1002/ana.410390210
61. Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., et al. (2008). TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672. doi: 10.1126/science.1154584
62. Stoica, R., De Vos, K. J., Paillusson, S., Mueller, S., Sancho, R. M., Lau, K. F., et al. (2014). ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat. Commun. 5:3996. doi: 10.1038/ncomms4996
63. Su, X. W., Broach, J. R., Connor, J. R., Gerhard, G. S., and Simmons, Z. (2014). Genetic heterogeneity of amyotrophic lateral sclerosis: implications for clinical practice and research. Muscle Nerve 49, 786-803. doi: 10.1002/mus.24198
64. Tadic, V., Prell, T., Lautenschlaeger, J., and Grosskreutz, J. (2014). The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis. Front. Cell. Neurosci. 8:147. doi: 10.3389/fncel.2014.00147
65. Tang, T. S., Tu, H., Chan, E. Y., Maximov, A., Wang, Z., Wellington, C. L., et al. (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. doi: 10.1016/S0896-6273(03)00366-0
66. Tateno, M., Sadakata, H., Tanaka, M., Itohara, S., Shin, R. M., Miura, M., et al. (2004). Calcium-permeable AMPA receptors promote misfolding of mutant SOD1 protein and development of amyotrophic lateral sclerosis in a transgenic mouse model. Hum. Mol. Genet. 13, 2183-2196. doi: 10.1093/hmg/ddh246
67. Tortarolo, M., Grignaschi, G., Calvaresi, N., Zennaro, E., Spaltro, G., Colovic, M., et al. (2006). Glutamate AMPA receptors change in motor neurons of SOD1G93A transgenic mice and their inhibition by a noncompetitive antagonist ameliorates the progression of amytrophic lateral sclerosis-like disease. J. Neurosci. Res. 83, 134-146. doi: 10.1002/jnr.20715
68. Tradewell, M. L., Cooper, L. A., Minotti, S., and Durham, H. D. (2011). Calcium dysregulation, mitochondrial pathology and protein aggregation in a culture model of amyotrophic lateral sclerosis: mechanistic relationship and differential sensitivity to intervention. Neurobiol. Dis. 42, 265-275. doi: 10.1016/j.nbd.2011.01.016
69. Tudor, E. L., Galtrey, C. M., Perkinton, M. S., Lau, K. F., De Vos, K. J., Mitchell, J. C., et al. (2010). Amyotrophic lateral sclerosis mutant vesicle-associated membrane protein-associated protein-B transgenic mice develop TAR-DNA-binding protein-43 pathology. Neuroscience 167, 774-785. doi: 10.1016/j.neuroscience.2010.02.035
70. Valencia, C. A., Ju, W., and Liu, R. (2007). Matrin 3 is a Ca2+/calmodulin-binding protein cleaved by caspases. Biochem. Biophys. Res. Commun. 361, 281-286. doi: 10.1016/j.bbrc.2007.06.156
71. Vance, C., Rogelj, B., Hortobágyi, T., De Vos, K. J., Nishimura, A. L., Sreedharan, J., et al. (2009). Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211. doi: 10.1126/science.1165942
72. Van Damme, P., Leyssen, M., Callewaert, G., Robberecht, W., and Van Den Bosch, L. (2003). The AMPA receptor antagonist NBQX prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci. Lett. 343, 81-84. doi: 10.1016/s0304-3940(03)00314-8
73. Vandenberghe, W., Robberecht, W., and Brorson, J. R. (2000). AMPA receptor calcium permeability, GluR2 expression and selective motoneuron vulnerability. J. Neurosci. 20, 123-132
74. Van Den Bosch, L., Vandenberghe, W., Klaassen, H., Van Houtte, E., and Robberecht, W. (2000). Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. J. Neurol. Sci. 180, 29-34. doi: 10.1016/s0022-510x(00)00414-7
75. van den Heuvel, D. M., Harschnitz, O., Van Den Berg, L. H., and Pasterkamp, R. J. (2014). Taking a risk: a therapeutic focus on ataxin-2 in amyotrophic lateral sclerosis? Trends Mol. Med. 20, 25-35. doi: 10.1016/j.molmed.2013.09.001
76. Vande Velde, C., Miller, T. M., Cashman, N. R., and Cleveland, D. W. (2008). Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria. Proc. Natl. Acad. Sci. U S A 105, 4022-4027. doi: 10.1073/pnas.0712209105
77. Volkening, K., Leystra-Lantz, C., Yang, W., Jaffee, H., and Strong, M. J. (2009). Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Res. 1305, 168-182. doi: 10.1016/j.brainres.2009.09.105
78. von Lewinski, F., and Keller, B. U. (2005). Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS. Trends Neurosci. 28, 494-500. doi: 10.1016/j.tins.2005.07.001
79. Wang, H. G., Pathan, N., Ethell, I. M., Krajewski, S., Yamaguchi, Y., Shibasaki, F., et al. (1999). Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 284, 339-343. doi: 10.1126/science.284.5412.339
80. Williams, T. L., Day, N. C., Ince, P. G., Kamboj, R. K., and Shaw, P. J. (1997). Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Ann. Neurol. 42, 200-207. doi: 10.1002/ana.410420211
81. Wu, C. H., Fallini, C., Ticozzi, N., Keagle, P. J., Sapp, P. C., Piotrowska, K., et al. (2012). Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488, 499-503. doi: 10.1038/nature11280
82. Yamashita, T., and Kwak, S. (2014). The molecular link between inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in motor neurons of sporadic amyotrophic lateral sclerosis patients. Brain Res. 1584, 28-38. doi: 10.1016/j.brainres.2013.12.011
83. Yin, H. Z., Tang, D. T., and Weiss, J. H. (2007). Intrathecal infusion of a Ca(2+)- permeable AMPA channel blocker slows loss of both motor neurons and of the astrocyte glutamate transporter, GLT-1 in a mutant SOD1 rat model of ALS. Exp. Neurol. 207, 177-185. doi: 10.1016/j.expneurol.2007.07.011
84. Zhang, M. D., Tortoriello, G., Hsueh, B., Tomer, R., Ye, L., Mitsios, N., et al. (2014). Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury. Proc. Natl. Acad. Sci. U S A 111, E1149-E1158. doi: 10.1073/pnas.1402318111
85. Zundorf, G., and Reiser, G. (2011). Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxid. Redox Signal. 14, 1275-1288. doi: 10.1089/ars.2010.3359