{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T07:47:03Z","timestamp":1778140023250,"version":"3.51.4"},"reference-count":169,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T00:00:00Z","timestamp":1648339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council of Hong Kong","award":["N_HKUST613\/17"],"award-info":[{"award-number":["N_HKUST613\/17"]}]},{"name":"Research Grants Council of Hong Kong","award":["A-HKUST603\/17"],"award-info":[{"award-number":["A-HKUST603\/17"]}]},{"DOI":"10.13039\/501100003452","name":"Innovation and Technology Commission","doi-asserted-by":"publisher","award":["ITCPD\/17-9"],"award-info":[{"award-number":["ITCPD\/17-9"]}],"id":[{"id":"10.13039\/501100003452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>\u03b1-synuclein (\u03b1-syn) is a presynaptic, lipid-binding protein strongly associated with the neuropathology observed in Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB), and Alzheimer\u2019s Disease (AD). In normal physiology, \u03b1-syn plays a pivotal role in facilitating endocytosis and exocytosis. Interestingly, mutations and modifications of precise \u03b1-syn domains interfere with \u03b1-syn oligomerization and nucleation that negatively affect presynaptic vesicular dynamics, protein expressions, and mitochondrial profiles. Furthermore, the integration of the \u03b1-syn oligomers into the presynaptic membrane results in pore formations, ion influx, and excitotoxicity. Targeted therapies against specific domains of \u03b1-syn, including the use of small organic molecules, monoclonal antibodies, and synthetic peptides, are being screened and developed. However, the prospect of an effective \u03b1-syn targeted therapy is still plagued by low permeability across the blood\u2013brain barrier (BBB), and poor entry into the presynaptic axon terminals. The present review proposes a modification of current strategies, which includes the use of novel encapsulation technology, such as lipid nanoparticles, to bypass the BBB and deliver such agents into the brain.<\/jats:p>","DOI":"10.3390\/biom12040507","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["\u03b1-Synuclein at the Presynaptic Axon Terminal as a Double-Edged Sword"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-4015","authenticated-orcid":false,"given":"Li Yang","family":"Tan","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore"},{"name":"Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwan Hou","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore"},{"name":"Faculty of Science, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynette Yu You","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore"},{"name":"Faculty of Science, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia Xin","family":"Ong","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore"},{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyokeun","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong"},{"name":"Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong"},{"name":"State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangyong","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.parkreldis.2015.09.007","article-title":"Autosomal dominant Parkinson\u2019s disease caused by SNCA duplications","volume":"22","author":"Konno","year":"2016","journal-title":"Park. 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