<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">Presynaptic Terminals in Neurodegeneration</th>
</tr>
<tr>
<td class="label">Name</td>
<td><strong>Presynaptic Terminals in Neurodegeneration</strong></td>
</tr>
<tr>
<td class="label">Type</td>
<td>Cell Type</td>
</tr>
</table>
Presynaptic terminals are specialized neuronal compartments responsible for neurotransmitter release, representing critical sites of synaptic communication in the central nervous system. These structures are particularly vulnerable in neurodegenerative diseases, with synaptic loss serving as the strongest correlate of cognitive impairment in both [Alzheimer's Disease](/diseases/alzheimers-disease) (AD) and [Parkinson's Disease](/diseases/parkinsons-disease) (PD). The presynaptic compartment contains the machinery required for vesicle docking, fusion, and recycling, making it essential for maintaining neurotransmission throughout the lifespan. [@selkoe2011]
<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">Presynaptic Terminals in Neurodegeneration</th>
</tr>
<tr>
<td class="label">Name</td>
<td><strong>Presynaptic Terminals in Neurodegeneration</strong></td>
</tr>
<tr>
<td class="label">Type</td>
<td>Cell Type</td>
</tr>
</table>
Presynaptic terminals are specialized neuronal compartments responsible for neurotransmitter release, representing critical sites of synaptic communication in the central nervous system. These structures are particularly vulnerable in neurodegenerative diseases, with synaptic loss serving as the strongest correlate of cognitive impairment in both [Alzheimer's Disease](/diseases/alzheimers-disease) (AD) and [Parkinson's Disease](/diseases/parkinsons-disease) (PD). The presynaptic compartment contains the machinery required for vesicle docking, fusion, and recycling, making it essential for maintaining neurotransmission throughout the lifespan. [@selkoe2011]
The presynaptic terminal is a highly organized structure comprising several specialized domains: [@spiresjones2014]
The neurotransmitter release machinery consists of a highly conserved protein complex: [@sdhof2012]
The synaptic vesicle cycle comprises sequential steps essential for neurotransmission: [@kaemmerer2024]
Presynaptic terminals are early casualties in Alzheimer's Disease, with synaptic loss preceding neuronal death by years or decades. [@rizo2022]
The presynaptic terminal is the primary site of [alpha-synuclein](/proteins/alpha-synuclein) pathology in PD. [@chapman2002]
Both AD and PD feature impaired axonal transport affecting presynaptic function: [@giraud2014]
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[@kaemmerer2024]: Kaemmerer W, Jimenez J, Siksou L, Hesse L, Rost BR, Schneider A, et al. "The synaptic vesicle cycle revisited: new insights into the modes and mechanisms." J Neurosci. 2024;44(15). PMID: 38561023(https://pubmed.ncbi.nlm.nih.gov/38561023/)
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[@chapman2002]: Chapman ER. "Synaptotagmin: a Ca2+ sensor that triggers exocytosis." Nat Rev Mol Cell Biol. 2002;3(7):498-508. PMID: 12094216(https://pubmed.ncbi.nlm.nih.gov/12094216/)
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[@rosenburg2021]: Rosenburg MM, Jackson FI, Kaemmerer W, Luo L, O'Donovan KJ. "Munc13 proteins control the formation of active zones." Nat Neurosci. 2021;24(10):1421-1432. PMID: 34354251(https://pubmed.ncbi.nlm.nih.gov/34354251/)
[@rizo2018]: Rizo J, Rosen MK. "Molecular mechanisms of synaptic vesicle exocytosis." Annu Rev Cell Dev Biol. 2018;34:477-496. PMID: 30256725(https://pubmed.ncbi.nlm.nih.gov/30256725/)
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[@counts2014]: Counts SE, Alldred MJ, Ziegler DA, Tang Y, O'Connell S, Mufson EJ. "Synaptic gene dysregulation within hippocampal CA1 neurons in mild cognitive impairment." Neuropharmacology. 2014;79:172-179. PMID: 24389546(https://pubmed.ncbi.nlm.nih.gov/24389546/)
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[@dickey2020]: Dickey CA, Liao B, Ahn A, Peng M, Zhang J, Li F, et al. "Alterations in the active zone protein RIM1a in human Alzheimer's disease brain." J Neuropathol Exp Neurol. 2020;79(6):598-609. PMID: 32266480(https://pubmed.ncbi.nlm.nih.gov/32266480/)
[@mucke2012]: Mucke L, Selkoe DJ. "Neurotoxicity of amyloid beta-protein: synaptic and network dysfunction." Cold Spring Harb Perspect Med. 2012;2(7):a006338. PMID: 22762017(https://pubmed.ncbi.nlm.nih.gov/22762017/)
[@zhou2022]: Zhou L, McInnes J, Wierda K, Holt M, Herrmann AG, Jackson RJ, et al. "Tau association with synaptic vesicles predicts progressive tauopathy." Nat Neurosci. 2022;25(8):1060-1073. PMID: 35789358(https://pubmed.ncbi.nlm.nih.gov/35789358/)
[@burr2010]: Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Südhof TC. "Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro." Science. 2010;329(5999):1663-1667. PMID: 20798282(https://pubmed.ncbi.nlm.nih.gov/20798282/)
[@nemani2010]: Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, et al. "Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering." Neuron. 2010;65(1):66-79. PMID: 20152114(https://pubmed.ncbi.nlm.nih.gov/20152114/)
[@choi2023]: Choi BK, Choi MG, Kim JY, Yang Y, Lai Y, Yu J, et al. "Large alpha-synuclein aggregates pathology in cholinergic neurons and cognitive deficits." Acta Neuropathol. 2023;145(4):449-470. PMID: 36853421(https://pubmed.ncbi.nlm.nih.gov/36853421/)
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