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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Synapses in neurodegenerative diseases

  • Bae, Jae Ryul (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Kim, Sung Hyun (Department of Physiology, School of Medicine, Kyung Hee University)
  • Received : 2017.03.07
  • Published : 2017.05.31
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Abstract

Synapse is the basic structural and functional component for neural communication in the brain. The presynaptic terminal is the structural and functionally essential area that initiates communication and maintains the continuous functional neural information flow. It contains synaptic vesicles (SV) filled with neurotransmitters, an active zone for release, and numerous proteins for SV fusion and retrieval. The structural and functional synaptic plasticity is a representative characteristic; however, it is highly vulnerable to various pathological conditions. In fact, synaptic alteration is thought to be central to neural disease processes. In particular, the alteration of the structural and functional phenotype of the presynaptic terminal is a highly significant evidence for neural diseases. In this review, we specifically describe structural and functional alteration of nerve terminals in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD).

Keywords

References

  1. Ikin AF, Annaert WG, Takei K et al (1996) Alzheimer amyloid protein precursor is localized in nerve terminal preparations to Rab5-containing vesicular organelles distinct from those implicated in the synaptic vesicle pathway. J Biol Chem 271, 31783-31786 https://doi.org/10.1074/jbc.271.50.31783
  2. Groemer TW, Thiel CS, Holt M et al (2011) Amyloid precursor protein is trafficked and secreted via synaptic vesicles. PLoS One 6, e18754 https://doi.org/10.1371/journal.pone.0018754
  3. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA and Herms J (2006) Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci 26, 7212-7221 https://doi.org/10.1523/JNEUROSCI.1450-06.2006
  4. Lassek M, Weingarten J, Wegner M et al (2016) APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone. PLoS Comput Biol 12, e1004832 https://doi.org/10.1371/journal.pcbi.1004832
  5. Jang BG, In S, Choi B and Kim MJ (2014) Beta-amyloid oligomers induce early loss of presynaptic proteins in primary neurons by caspase-dependent and proteasomedependent mechanisms. Neuroreport 25, 1281-1288 https://doi.org/10.1097/WNR.0000000000000260
  6. Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E and Slutsky I (2009) Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci 12, 1567-1576 https://doi.org/10.1038/nn.2433
  7. Fogel H, Frere S, Segev O et al (2014) APP homodimers transduce an amyloid-beta-mediated increase in release probability at excitatory synapses. Cell Rep 7, 1560-1576 https://doi.org/10.1016/j.celrep.2014.04.024
  8. Romani A, Marchetti C, Bianchi D et al (2013) Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses. Front Comput Neurosci 7, 1
  9. Russell CL, Semerdjieva S, Empson RM, Austen BM, Beesley PW and Alifragis P (2012) Amyloid-beta acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2. PLoS One 7, e43201 https://doi.org/10.1371/journal.pone.0043201
  10. Cirrito JR, Yamada KA, Finn MB et al (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48, 913-922 https://doi.org/10.1016/j.neuron.2005.10.028
  11. Cirrito JR, Kang JE, Lee J et al (2008) Endocytosis is required for synaptic activity-dependent release of amyloidbeta in vivo. Neuron 58, 42-51 https://doi.org/10.1016/j.neuron.2008.02.003
  12. Munro KM, Nash A, Pigoni M, Lichtenthaler SF and Gunnersen JM (2016) Functions of the Alzheimer's Disease Protease BACE1 at the Synapse in the Central Nervous System. J Mol Neurosci 60, 305-315 https://doi.org/10.1007/s12031-016-0800-1
  13. Lundgren JL, Ahmed S, Schedin-Weiss S et al (2015) ADAM10 and BACE1 are localized to synaptic vesicles. J Neurochem 135, 606-615 https://doi.org/10.1111/jnc.13287
  14. Del Prete D, Lombino F, Liu X and D'Adamio L (2014) APP is cleaved by Bace1 in pre-synaptic vesicles and establishes a pre-synaptic interactome, via its intracellular domain, with molecular complexes that regulate presynaptic vesicles functions. PLoS One 9, e108576 https://doi.org/10.1371/journal.pone.0108576
  15. Petrus E and Lee HK (2014) BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex. Neural Plast 2014, 128631
  16. Frykman S, Hur JY, Franberg J et al (2010) Synaptic and endosomal localization of active gamma-secretase in rat brain. PLoS One 5, e8948 https://doi.org/10.1371/journal.pone.0008948
  17. Zhang C, Wu B, Beglopoulos V et al (2009) Presenilins are essential for regulating neurotransmitter release. Nature 460, 632-636 https://doi.org/10.1038/nature08177
  18. Pratt KG, Zimmerman EC, Cook DG and Sullivan JM (2011) Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling. Nat Neurosci 14, 1112-1114 https://doi.org/10.1038/nn.2893
  19. Spires-Jones TL and Hyman BT (2014) The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 82, 756-771 https://doi.org/10.1016/j.neuron.2014.05.004
  20. Voelzmann A, Okenve-Ramos P, Qu Y et al (2016) Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking. Elife 5
  21. Jadhav S, Katina S, Kovac A, Kazmerova Z, Novak M and Zilka N (2015) Truncated tau deregulates synaptic markers in rat model for human tauopathy. Front Cell Neurosci 9, 24
  22. Kopeikina KJ, Polydoro M, Tai HC et al (2013) Synaptic alterations in the rTg4510 mouse model of tauopathy. J Comp Neurol 521, 1334-1353 https://doi.org/10.1002/cne.23234
  23. Kopeikina KJ, Wegmann S, Pitstick R et al (2013) Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy. PLoS One 8, e80834 https://doi.org/10.1371/journal.pone.0080834
  24. Levi O, Jongen-Relo AL, Feldon J, Roses AD and Michaelson DM (2003) ApoE4 impairs hippocampal plasticity isoform-specifically and blocks the environmental stimulation of synaptogenesis and memory. Neurobiol Dis 13, 273-282 https://doi.org/10.1016/S0969-9961(03)00045-7
  25. Zhu Y, Nwabuisi-Heath E, Dumanis SB et al (2012) APOE genotype alters glial activation and loss of synaptic markers in mice. Glia 60, 559-569 https://doi.org/10.1002/glia.22289
  26. Cambon K, Davies HA and Stewart MG (2000) Synaptic loss is accompanied by an increase in synaptic area in the dentate gyrus of aged human apolipoprotein E4 transgenic mice. Neuroscience 97, 685-692 https://doi.org/10.1016/S0306-4522(00)00065-8
  27. Dumanis SB, DiBattista AM, Miessau M, Moussa CE and Rebeck GW (2013) APOE genotype affects the presynaptic compartment of glutamatergic nerve terminals. J Neurochem 124, 4-14 https://doi.org/10.1111/j.1471-4159.2012.07908.x
  28. Bal M, Leitz J, Reese AL et al (2013) Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission. Neuron 80, 934-946 https://doi.org/10.1016/j.neuron.2013.08.024
  29. Koffie RM, Hashimoto T, Tai HC et al (2012) Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-beta. Brain 135, 2155-2168 https://doi.org/10.1093/brain/aws127
  30. Picconi B, Piccoli G and Calabresi P (2012) Synaptic dysfunction in Parkinson's disease. Adv Exp Med Biol 970, 553-572
  31. Belluzzi E, Greggio E and Piccoli G (2012) Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2. Biochem Soc Trans 40, 1111-1116 https://doi.org/10.1042/BST20120124
  32. Stefanis L (2012) alpha-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med 2, a009399
  33. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2, 492-501 https://doi.org/10.1038/35081564
  34. Norris EH, Giasson BI and Lee VM (2004) Alphasynuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol 60, 17-54
  35. Rizo J and Sudhof TC (2012) The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged? Annu Rev Cell Dev Biol 28, 279-308 https://doi.org/10.1146/annurev-cellbio-101011-155818
  36. Tanji K, Mori F, Mimura J et al (2010) Proteinase K-resistant alpha-synuclein is deposited in presynapses in human Lewy body disease and A53T alpha-synuclein transgenic mice. Acta Neuropathol 120, 145-154 https://doi.org/10.1007/s00401-010-0676-z
  37. Spinelli KJ, Taylor JK, Osterberg VR et al (2014) Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson's disease. J Neurosci 34, 2037-2050 https://doi.org/10.1523/JNEUROSCI.2581-13.2014
  38. Lundblad M, Decressac M, Mattsson B and Bjorklund A (2012) Impaired neurotransmission caused by overexpression of alpha-synuclein in nigral dopamine neurons. Proc Natl Acad Sci U S A 109, 3213-3219 https://doi.org/10.1073/pnas.1200575109
  39. Xu J, Wu XS, Sheng J et al (2016) alpha-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve Terminals. J Neurosci 36, 4408-4414 https://doi.org/10.1523/JNEUROSCI.3627-15.2016
  40. Nemani VM, Lu W, Berge V et al (2010) Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65, 66-79 https://doi.org/10.1016/j.neuron.2009.12.023
  41. Scott D and Roy S (2012) alpha-Synuclein inhibits intersynaptic vesicle mobility and maintains recyclingpool homeostasis. J Neurosci 32, 10129-10135 https://doi.org/10.1523/JNEUROSCI.0535-12.2012
  42. Mills RD, Mulhern TD, Liu F, Culvenor JG and Cheng HC (2014) Prediction of the repeat domain structures and impact of parkinsonism-associated variations on structure and function of all functional domains of leucine-rich repeat kinase 2 (LRRK2). Hum Mutat 35, 395-412 https://doi.org/10.1002/humu.22515
  43. Martin I, Kim JW, Dawson VL and Dawson TM (2014) LRRK2 pathobiology in Parkinson's disease. J Neurochem 131, 554-565 https://doi.org/10.1111/jnc.12949
  44. Lee S, Liu HP, Lin WY, Guo H and Lu B (2010) LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. J Neurosci 30, 16959-16969 https://doi.org/10.1523/JNEUROSCI.1807-10.2010
  45. Matta S, Van Kolen K, da Cunha R et al (2012) LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron 75, 1008-1021 https://doi.org/10.1016/j.neuron.2012.08.022
  46. Arranz AM, Delbroek L, Van Kolen K et al (2015) LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci 128, 541-552 https://doi.org/10.1242/jcs.158196
  47. Belluzzi E, Gonnelli A, Cirnaru MD et al (2016) LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate. Mol Neurodegener 11, 1 https://doi.org/10.1186/s13024-015-0066-z
  48. Li X, Patel JC, Wang J et al (2010) Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S. J Neurosci 30, 1788-1797 https://doi.org/10.1523/JNEUROSCI.5604-09.2010
  49. Beccano-Kelly DA, Kuhlmann N, Tatarnikov I et al (2014) Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci 8, 301
  50. Beccano-Kelly DA, Volta M, Munsie LN et al (2015) LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory. Hum Mol Genet 24, 1336-1349 https://doi.org/10.1093/hmg/ddu543
  51. Leroy E, Anastasopoulos D, Konitsiotis S, Lavedan C and Polymeropoulos MH (1998) Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson's disease. Hum Genet 103, 424-427 https://doi.org/10.1007/s004390050845
  52. Lucking CB, Abbas N, Durr A et al (1998) Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism. The European Consortium on Genetic Susceptibility in Parkinson's Disease and the French Parkinson's Disease Genetics Study Group. Lancet 352, 1355-1356 https://doi.org/10.1016/S0140-6736(05)60746-5
  53. Kitada T, Pisani A, Karouani M et al (2009) Impaired dopamine release and synaptic plasticity in the striatum of parkin-/- mice. J Neurochem 110, 613-621 https://doi.org/10.1111/j.1471-4159.2009.06152.x
  54. Helton TD, Otsuka T, Lee MC, Mu Y and Ehlers MD (2008) Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Proc Natl Acad Sci U S A 105, 19492-19497 https://doi.org/10.1073/pnas.0802280105
  55. Cortese GP, Zhu M, Williams D, Heath S and Waites CL (2016) Parkin Deficiency Reduces Hippocampal Glutamatergic Neurotransmission by Impairing AMPA Receptor Endocytosis. J Neurosci 36, 12243-12258 https://doi.org/10.1523/JNEUROSCI.1473-16.2016
  56. Khandelwal PJ, Dumanis SB, Feng LR et al (2010) Parkinson-related parkin reduces alpha-Synuclein phosphorylation in a gene transfer model. Mol Neurodegener 5, 47 https://doi.org/10.1186/1750-1326-5-47
  57. Zhang Y, Gao J, Chung KK, Huang H, Dawson VL and Dawson TM (2000) Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A 97, 13354-13359 https://doi.org/10.1073/pnas.240347797
  58. Chung KK, Zhang Y, Lim KL et al (2001) Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med 7, 1144-1150 https://doi.org/10.1038/nm1001-1144
  59. Valente EM, Abou-Sleiman PM, Caputo V et al (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158-1160 https://doi.org/10.1126/science.1096284
  60. Beilina A, Van Der Brug M, Ahmad R et al (2005) Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A 102, 5703-5708 https://doi.org/10.1073/pnas.0500617102
  61. Plun-Favreau H, Klupsch K, Moisoi N et al (2007) The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat Cell Biol 9, 1243-1252 https://doi.org/10.1038/ncb1644
  62. Morais VA, Verstreken P, Roethig A et al (2009) Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med 1, 99-111 https://doi.org/10.1002/emmm.200900006
  63. Xi Y, Ryan J, Noble S, Yu M, Yilbas AE and Ekker M (2010) Impaired dopaminergic neuron development and locomotor function in zebrafish with loss of pink1 function. Eur J Neurosci 31, 623-633 https://doi.org/10.1111/j.1460-9568.2010.07091.x
  64. Kitada T, Pisani A, Porter DR et al (2007) Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci U S A 104, 11441-11446 https://doi.org/10.1073/pnas.0702717104
  65. Junn E, Jang WH, Zhao X, Jeong BS and Mouradian MM (2009) Mitochondrial localization of DJ-1 leads to enhanced neuroprotection. J Neurosci Res 87, 123-129 https://doi.org/10.1002/jnr.21831
  66. Bonifati V, Rizzu P, van Baren MJ et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256-259 https://doi.org/10.1126/science.1077209
  67. Usami Y, Hatano T, Imai S et al (2011) DJ-1 associates with synaptic membranes. Neurobiol Dis 43, 651-662 https://doi.org/10.1016/j.nbd.2011.05.014
  68. Goldberg MS, Pisani A, Haburcak M et al (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-496 https://doi.org/10.1016/j.neuron.2005.01.041
  69. Slepnev VI and De Camilli P (2000) Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci 1, 161-172
  70. McPherson PS, Garcia EP, Slepnev VI et al (1996) A presynaptic inositol-5-phosphatase. Nature 379, 353-357 https://doi.org/10.1038/379353a0
  71. Mani M, Lee SY, Lucast L et al (2007) The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals. Neuron 56, 1004-1018 https://doi.org/10.1016/j.neuron.2007.10.032
  72. Krebs CE, Karkheiran S, Powell JC 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 https://doi.org/10.1002/humu.22372
  73. Quadri M, Fang M, Picillo M et al (2013) Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum Mutat 34, 1208-1215 https://doi.org/10.1002/humu.22373
  74. Hardies K, Cai Y, Jardel C et al (2016) Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline. Brain 139, 2420-2430 https://doi.org/10.1093/brain/aww180
  75. Cao M, Wu Y, Ashrafi G et al (2017) Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons. Neuron 93, 882-896 e885 https://doi.org/10.1016/j.neuron.2017.01.019
  76. Cao M, Milosevic I, Giovedi S and De Camilli P (2014) Upregulation of Parkin in endophilin mutant mice. J Neurosci 34, 16544-16549 https://doi.org/10.1523/JNEUROSCI.1710-14.2014
  77. Schuske KR, Richmond JE, Matthies DS et al (2003) Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin. Neuron 40, 749-762 https://doi.org/10.1016/S0896-6273(03)00667-6
  78. Soukup SF, Kuenen S, Vanhauwaert R et al (2016) A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals. Neuron 92, 829-844 https://doi.org/10.1016/j.neuron.2016.09.037
  79. Felbecker A, Camu W, Valdmanis PN et al (2010) Four familial ALS pedigrees discordant for two SOD1 mutations: are all SOD1 mutations pathogenic? J Neurol Neurosurg Psychiatry 81, 572-577 https://doi.org/10.1136/jnnp.2009.192310
  80. Robberecht W, Aguirre T, Van den Bosch L, Tilkin P, Cassiman JJ and Matthijs G (1996) D90A heterozygosity in the SOD1 gene is associated with familial and apparently sporadic amyotrophic lateral sclerosis. Neurology 47, 1336-1339 https://doi.org/10.1212/WNL.47.5.1336
  81. Andersen PM (2006) Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep 6, 37-46 https://doi.org/10.1007/s11910-996-0008-9
  82. Lee DY, Jeon GS, Shim YM, Seong SY, Lee KW and Sung JJ (2015) Modulation of SOD1 Subcellular Localization by Transfection with Wild- or Mutant-type SOD1 in Primary Neuron and Astrocyte Cultures from ALS Mice. Exp Neurobiol 24, 226-234 https://doi.org/10.5607/en.2015.24.3.226
  83. Bae JR and Kim SH (2016) Impairment of SOD1-G93A motility is linked to mitochondrial movement in axons of hippocampal neurons. Arch Pharm Res 39, 1144-1150 https://doi.org/10.1007/s12272-016-0798-5
  84. Tallon C, Russell KA, Sakhalkar S, Andrapallayal N and Farah MH (2016) Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice. Neuroscience 312, 179-189 https://doi.org/10.1016/j.neuroscience.2015.11.018
  85. Zang DW, Lopes EC and Cheema SS (2005) Loss of synaptophysin-positive boutons on lumbar motor neurons innervating the medial gastrocnemius muscle of the SOD1G93A G1H transgenic mouse model of ALS. J Neurosci Res 79, 694-699 https://doi.org/10.1002/jnr.20379
  86. Gregory RI, Yan KP, Amuthan G et al (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235-240 https://doi.org/10.1038/nature03120
  87. Xu ZS (2012) Does a loss of TDP-43 function cause neurodegeneration? Mol Neurodegener 7, 27 https://doi.org/10.1186/1750-1326-7-27
  88. Medina DX, Orr ME and Oddo S (2014) Accumulation of C-terminal fragments of transactive response DNA-binding protein 43 leads to synaptic loss and cognitive deficits in human TDP-43 transgenic mice. Neurobiol Aging 35, 79-87 https://doi.org/10.1016/j.neurobiolaging.2013.07.006
  89. Handley EE, Pitman KA, Dawkins E et al (2016) Synapse Dysfunction of Layer V Pyramidal Neurons Precedes Neurodegeneration in a Mouse Model of TDP-43 Proteinopathies. Cereb Cortex 1-18
  90. Nolan M, Talbot K and Ansorge O (2016) Pathogenesis of FUS-associated ALS and FTD: insights from rodent models. Acta Neuropathol Commun 4, 99 https://doi.org/10.1186/s40478-016-0358-8
  91. Da Cruz S and Cleveland DW (2011) Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr Opin Neurobiol 21, 904-919 https://doi.org/10.1016/j.conb.2011.05.029
  92. Lagier-Tourenne C and Cleveland DW (2009) Rethinking ALS: the FUS about TDP-43. Cell 136, 1001-1004 https://doi.org/10.1016/j.cell.2009.03.006
  93. Machamer JB, Collins SE and Lloyd TE (2014) The ALS gene FUS regulates synaptic transmission at the Drosophila neuromuscular junction. Hum Mol Genet 23, 3810-3822 https://doi.org/10.1093/hmg/ddu094
  94. Romero E, Cha GH, Verstreken P et al (2008) Suppression of neurodegeneration and increased neurotransmission caused by expanded full-length huntingtin accumulating in the cytoplasm. Neuron 57, 27-40 https://doi.org/10.1016/j.neuron.2007.11.025
  95. Deak F, Shin OH, Tang J et al (2006) Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion. EMBO J 25, 2856-2866 https://doi.org/10.1038/sj.emboj.7601165
  96. Parker JA, Metzler M, Georgiou J et al (2007) Huntingtininteracting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity. J Neurosci 27, 11056-11064 https://doi.org/10.1523/JNEUROSCI.1941-07.2007

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