{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent structural investigations have revealed that SV2C, a member of the synaptic vesicle glycoprotein 2 family, plays a critical role as a receptor for botulinum neurotoxin serotype A (BoNT/A). High‐resolution crystal structures have demonstrated that the luminal domain of SV2C—featuring both peptide determinants and a conserved N‐linked glycan—is essential for robust BoNT/A binding and subsequent neuronal uptake, thereby underpinning the toxin’s potent neuroparalytic action. These insights provide a strong rationale for targeting the SV2C–BoNT/A interface in the development of novel antitoxin strategies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in mediating toxin entry, SV2C is emerging as a central regulator of dopamine neurotransmission within the basal ganglia. Experimental models have demonstrated that loss or disrupted expression of SV2C leads to impaired dopamine release, decreased striatal dopamine levels, altered expression of α‐synuclein, and motor deficits—findings that are particularly relevant to the pathophysiology of Parkinson’s disease. Genome‐wide association studies further implicate genetic variants linked to PD risk, reinforcing the notion that SV2C is critical for the homeostasis of dopaminergic neurons."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these functions, research into the pharmacogenetics and expression patterns of synaptic vesicle proteins has begun to delineate additional roles for SV2C in the central nervous system. While studies of genetic variation in SV2C have not yet revealed strong predictive associations with responses to antiepileptic or antipsychotic drugs, its restricted expression—demonstrated in analyses of the hippocampus and human neuroblastoma cell lines—points to a nuanced contribution to neurophysiological regulation and disease pathology in conditions such as temporal lobe epilepsy. Such findings underscore the potential for SV2C to serve as a biomarker or therapeutic target across a range of neuropsychiatric disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Roger M Benoit, Daniel Frey, Manuel Hilbert, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1616892114"}], "href": "https://doi.org/10.1073/pnas.1616892114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28246328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28246328"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jia Nee Foo, Elaine Guo Yan Chew, Sun Ju Chung, et al. 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