{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:24:13Z","timestamp":1791404653440,"version":"4.3.3"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC81571226"],"award-info":[{"award-number":["NSFC81571226"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82020108012"],"award-info":[{"award-number":["NSFC82020108012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC81671187"],"award-info":[{"award-number":["NSFC81671187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7232013"],"award-info":[{"award-number":["7232013"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011276","name":"Alzheimer\u2019s Disease Research Center, University of Washington","doi-asserted-by":"publisher","award":["AG05136"],"award-info":[{"award-number":["AG05136"]}],"id":[{"id":"10.13039\/100011276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), share a distinct pathological feature, that is, a widespread accumulation of \u03b1\u2010synuclein (\u03b1\u2010syn) in the brain. There is a significant clinical unmet need for disease\u2010modifying treatments for synucleinopathies. Recently, a seaweed\u2010derived mixture of oligosaccharides sodium oligomannate, GV\u2010971, was approved for Phase 2 clinical trials for PD. This study aimed to further evaluate the therapeutic effects of GV\u2010971 on synucleinopathies using cellular and animal models and explore its associated molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      \u03b1\u2010Syn aggregation was assessed, in vitro and ex vivo, by ThT assay. A dopaminergic neuron cell line,\n                      <jats:italic>Prnp\u2010SNCA<\/jats:italic>\n                      <jats:sup>A53T<\/jats:sup>\n                      mice, and brain slices from PD and DLB patients were used to determine the efficacy of GV\u2010971 in ameliorating \u03b1\u2010syn pathology. Measurements of motor functions, including pole, cylinder, and rotarod tests, were conducted on\n                      <jats:italic>Prnp\u2010SNCA<\/jats:italic>\n                      <jats:sup>A53T<\/jats:sup>\n                      mice 4\u2009weeks after intragastric administration of GV\u2010971 (200\u2009mg\u2009day\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GV\u2010971 effectively prevented \u03b1\u2010syn aggregation and even disassembled pre\u2010aggregated \u03b1\u2010syn fibrils, in vitro and ex vivo\n                      <jats:italic>.<\/jats:italic>\n                      In addition, GV\u2010971 was able to rescue \u03b1\u2010syn\u2010induced neuronal damage and reduced release of extracellular vesicles (EVs), likely via modulating Alix expression. In the\n                      <jats:italic>Prnp\u2010SNCA<\/jats:italic>\n                      <jats:sup>A53T<\/jats:sup>\n                      mouse model, when treated at the age of 5\u2009months, GV\u2010971 significantly decreased \u03b1\u2010syn deposition in the cortex, midbrain, and cerebellum regions, along with ameliorating the motor dysfunctions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results indicate that GV\u2010971, when administered at a relatively early stage of the disease process, significantly reduced \u03b1\u2010syn accumulation and aggregation in\n                      <jats:italic>Prnp\u2010SNCA<\/jats:italic>\n                      <jats:sup>A53T<\/jats:sup>\n                      mice. Furthermore, GV\u2010971 corrected \u03b1\u2010syn\u2010induced inhibition of EVs release in neurons, contributing to neuronal protection. Future studies are needed to further assess GV\u2010971 as a promising disease\u2010modifying therapy for PD and other synucleinopathies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14393","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T01:32:52Z","timestamp":1691717572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp>GV<\/scp>\n                    \u2010971 attenuates\n                    <scp>\u03b1\u2010Synuclein<\/scp>\n                    aggregation and related pathology"],"prefix":"10.1111","volume":"30","author":[{"given":"Zhenwei","family":"Yu","sequence":"first","affiliation":[{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, 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