Browse > Article
http://dx.doi.org/10.5483/BMBRep.2017.50.5.038

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)
Publication Information
BMB Reports / v.50, no.5, 2017 , pp. 237-246 More about this Journal
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
Alzheimer's disease; Neurotransmission; Parkinson's disease; Presynaptic terminals; Synaptic vesicle;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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   DOI
2 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   DOI
3 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   DOI
4 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
5 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   DOI
6 Cirrito JR, Yamada KA, Finn MB et al (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48, 913-922   DOI
7 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   DOI
8 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   DOI
9 Lundgren JL, Ahmed S, Schedin-Weiss S et al (2015) ADAM10 and BACE1 are localized to synaptic vesicles. J Neurochem 135, 606-615   DOI
10 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   DOI
11 Cao M, Milosevic I, Giovedi S and De Camilli P (2014) Upregulation of Parkin in endophilin mutant mice. J Neurosci 34, 16544-16549   DOI
12 Schuske KR, Richmond JE, Matthies DS et al (2003) Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin. Neuron 40, 749-762   DOI
13 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   DOI
14 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   DOI
15 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   DOI
16 Andersen PM (2006) Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep 6, 37-46   DOI
17 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   DOI
18 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   DOI
19 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   DOI
20 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   DOI
21 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   DOI
22 Gregory RI, Yan KP, Amuthan G et al (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235-240   DOI
23 Xu ZS (2012) Does a loss of TDP-43 function cause neurodegeneration? Mol Neurodegener 7, 27   DOI
24 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   DOI
25 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
26 Nolan M, Talbot K and Ansorge O (2016) Pathogenesis of FUS-associated ALS and FTD: insights from rodent models. Acta Neuropathol Commun 4, 99   DOI
27 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   DOI
28 Lagier-Tourenne C and Cleveland DW (2009) Rethinking ALS: the FUS about TDP-43. Cell 136, 1001-1004   DOI
29 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   DOI
30 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   DOI
31 Petrus E and Lee HK (2014) BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex. Neural Plast 2014, 128631
32 Frykman S, Hur JY, Franberg J et al (2010) Synaptic and endosomal localization of active gamma-secretase in rat brain. PLoS One 5, e8948   DOI
33 Zhang C, Wu B, Beglopoulos V et al (2009) Presenilins are essential for regulating neurotransmitter release. Nature 460, 632-636   DOI
34 Pratt KG, Zimmerman EC, Cook DG and Sullivan JM (2011) Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling. Nat Neurosci 14, 1112-1114   DOI
35 Spires-Jones TL and Hyman BT (2014) The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 82, 756-771   DOI
36 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
37 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
38 Kopeikina KJ, Polydoro M, Tai HC et al (2013) Synaptic alterations in the rTg4510 mouse model of tauopathy. J Comp Neurol 521, 1334-1353   DOI
39 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   DOI
40 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   DOI
41 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   DOI
42 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   DOI
43 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   DOI
44 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   DOI
45 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   DOI
46 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   DOI
47 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   DOI
48 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   DOI
49 Picconi B, Piccoli G and Calabresi P (2012) Synaptic dysfunction in Parkinson's disease. Adv Exp Med Biol 970, 553-572
50 Belluzzi E, Greggio E and Piccoli G (2012) Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2. Biochem Soc Trans 40, 1111-1116   DOI
51 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   DOI
52 Stefanis L (2012) alpha-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med 2, a009399
53 Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2, 492-501   DOI
54 Norris EH, Giasson BI and Lee VM (2004) Alphasynuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol 60, 17-54
55 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   DOI
56 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   DOI
57 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   DOI
58 Xu J, Wu XS, Sheng J et al (2016) alpha-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve Terminals. J Neurosci 36, 4408-4414   DOI
59 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   DOI
60 Scott D and Roy S (2012) alpha-Synuclein inhibits intersynaptic vesicle mobility and maintains recyclingpool homeostasis. J Neurosci 32, 10129-10135   DOI
61 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   DOI
62 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   DOI
63 Martin I, Kim JW, Dawson VL and Dawson TM (2014) LRRK2 pathobiology in Parkinson's disease. J Neurochem 131, 554-565   DOI
64 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   DOI
65 Matta S, Van Kolen K, da Cunha R et al (2012) LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron 75, 1008-1021   DOI
66 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   DOI
67 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   DOI
68 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
69 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   DOI
70 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   DOI
71 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   DOI
72 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   DOI
73 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   DOI
74 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   DOI
75 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   DOI
76 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   DOI
77 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   DOI
78 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   DOI
79 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   DOI
80 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   DOI
81 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   DOI
82 Usami Y, Hatano T, Imai S et al (2011) DJ-1 associates with synaptic membranes. Neurobiol Dis 43, 651-662   DOI
83 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   DOI
84 Groemer TW, Thiel CS, Holt M et al (2011) Amyloid precursor protein is trafficked and secreted via synaptic vesicles. PLoS One 6, e18754   DOI
85 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   DOI
86 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   DOI
87 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   DOI
88 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   DOI
89 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   DOI
90 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   DOI
91 Slepnev VI and De Camilli P (2000) Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci 1, 161-172
92 McPherson PS, Garcia EP, Slepnev VI et al (1996) A presynaptic inositol-5-phosphatase. Nature 379, 353-357   DOI
93 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   DOI
94 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   DOI
95 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   DOI
96 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   DOI