{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:48:44Z","timestamp":1792180124290,"version":"4.4.0"},"reference-count":51,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Synaptic vesicle fusion is a process that involves the release of neurotransmitters from synaptic vesicles into the synaptic cleft.\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    is a protein that mediates synaptic vesicle fusion by forming a complex with other proteins on the presynaptic membrane. Mutations in\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    have been recently identified as a cause of a rare form of hereditary spastic paraplegia (HSP), a group of genetic disorders characterized by the gradual development of muscle stiffness and weakness in the lower extremities. We discuss the current knowledge on the structure and function of\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    and its role in synaptic transmission, the clinical features and genetic findings of patients with\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    mutations, the possible pathogenic mechanisms of\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    mutations, such as impaired SNARE complex formation, calcium signaling, and synaptic vesicle recycling and the potential therapeutic strategies for modulating\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    function and restoring synaptic vesicle fusion in hereditary spastic paraplegia patients. We also highlight the\n                    <jats:italic toggle=\"yes\">research<\/jats:italic>\n                    gaps and emerging technologies that may advance the understanding and treatment of\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    -related hereditary spastic paraplegia. Furthermore, the review presents some experimental studies that have investigated the molecular and functional consequences of\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    mutations in various models, such as mice, cell lines, or patient-derived samples. These studies have provided evidence for reduced or altered\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    expression, impaired synaptic vesicle fusion and neurotransmitter release, altered synaptic plasticity and excitability, and neuronal degeneration in\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    mutation carriers. These findings suggest that\n                    <jats:italic toggle=\"yes\">VAMP1<\/jats:italic>\n                    mutations have a significant impact on synaptic vesicle fusion dynamics and neuronal function and may contribute to the pathogenesis and phenotypic variability of hereditary spastic paraplegia.\n                  <\/jats:p>","DOI":"10.1177\/08830738251367467","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T13:43:38Z","timestamp":1756215818000},"page":"109-117","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of VAMP1 Mutations on Synaptic Vesicle Fusion Dynamics in Familial Spastic Disorders"],"prefix":"10.1177","volume":"41","author":[{"given":"Shifa","family":"Israr","sequence":"first","affiliation":[{"name":"Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-5800","authenticated-orcid":false,"given":"Muhammad","family":"Ikrama","sequence":"additional","affiliation":[{"name":"Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-7089","authenticated-orcid":false,"given":"Muhammad","family":"Usama","sequence":"additional","affiliation":[{"name":"Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Humayon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12524"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.04.001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.12.4538"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.09.025"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2024.04.027"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11030403"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031697"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"e_1_3_2_11_2","unstructured":"Hedera P. Uncomplicated (pure) hereditary spastic paraplegia overview. 2021. August 15 2000 [updated June 5 2025]. In: Adam MP Feldman J Mirzaa GM Pagon RA Wallace SE Amemiya A eds. GeneReviews\u00ae [Internet]. University of Washington Seattle; 1993\u20132025. 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In: Adam MP Feldman J Mirzaa GM et al. (eds) GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington Seattle; 1993\u20132025. 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