{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:41Z","timestamp":1787028581751,"version":"build-2736575974"},"reference-count":139,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005273","name":"Natural Science Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["202501AS070139"],"award-info":[{"award-number":["202501AS070139"]}],"id":[{"id":"10.13039\/501100005273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China\n\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["82060823"],"award-info":[{"award-number":["82060823"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China\n\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["81660671"],"award-info":[{"award-number":["81660671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007846","name":"Yunnan Provincial Department of Education\n\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/02yrxdp92","doi-asserted-by":"publisher","award":["2024Y395"],"award-info":[{"award-number":["2024Y395"]}],"id":[{"id":"10.13039\/501100007846","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Science and Technology Talent and Platform Program","award":["202105AG070012XS25032"],"award-info":[{"award-number":["202105AG070012XS25032"]}]},{"name":"Yunnan Collaborative Innovation Center for the Application of Aromatic Chinese Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s (AD) and Parkinson\u2019s disease (PD) are prominent neurodegenerative disorders characterized by early synaptic loss, which correlates more closely with clinical symptoms than neuronal death. This synaptic impairment is primarily driven by disruptions in synaptic vesicle (SV) trafficking, a critical process for maintaining synaptic integrity through a tightly regulated cycle involving clustering, docking-priming, Ca2+-triggered fusion, and endocytosis. In AD, amyloid-\u03b2 (A\u03b2) oligomers interfere with SNARE-mediated fusion and endocytosis, while hyperphosphorylated tau obstructs vesicle mobility and docking, resulting in cumulative toxicity that aggravates SV defects. Conversely, in PD, \u03b1-synuclein (\u03b1-syn) aggregation alters vesicle clustering, membrane fusion, and recycling, and these effects are further influenced by Leucine-rich repeat kinase 2 (LRRK2)-Rab-related trafficking defects and the selective vulnerability of dopaminergic terminals. Different from previous reviews that address synaptic dysfunction in a broader manner, the present review is specifically organized around the SV trafficking cycle and compares both shared presynaptic endpoints and disease-specific upstream mechanisms in AD and PD. In addition, recent mechanism-oriented therapeutic strategies are summarized. This vesicle-cycle-centered perspective may provide a clearer framework for understanding presynaptic pathology and for guiding the development of earlier and more targeted interventions.<\/jats:p>","DOI":"10.3390\/ijms27073089","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"3089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disruption of Synaptic Vesicle Trafficking in Alzheimer\u2019s and Parkinson\u2019s Disease: Mechanisms and Therapeutic Implication"],"prefix":"10.3390","volume":"27","author":[{"given":"Youyang","family":"Zhu","sequence":"first","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianna","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingming","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Tian","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingdi","family":"Liao","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqing","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Guo","sequence":"additional","affiliation":[{"name":"The College Based Key Laboratory of Yunnan in Aromatic Chinese Herbal Research, Kunming 650500, China"},{"name":"College of Ethnic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuan","family":"Xie","sequence":"additional","affiliation":[{"name":"The College Based Key Laboratory of Yunnan in Aromatic Chinese Herbal Research, Kunming 650500, China"},{"name":"Science and Technology Department, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1113\/jphysiol.1954.sp005129","article-title":"Quantal components of the end-plate potential","volume":"124","author":"Katz","year":"1954","journal-title":"J. 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