{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:02:26Z","timestamp":1779793346016,"version":"3.53.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transsynaptic \u03b1\u2010synuclein propagation plays a crucial role in the progression of Lewy body disease. We previously demonstrated that an \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptor antagonist, perampanel, blocks neuronal uptake of \u03b1\u2010synuclein preformed fibrils (PFFs) in an activity\u2010dependent manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to elucidate the underlying mechanisms of this effect and whether perampanel inhibits transsynaptic \u03b1\u2010synuclein propagation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Neuronal uptake of PFFs was evaluated in mouse primary hippocampal neurons using PFFs labeled with pH\u2010sensitive dye. The levels of dynamin1 and phosphorylated dynamin1 were analyzed in wild\u2010type mice treated with perampanel using western blotting. The time course of clearance of PFFs injected into the olfactory bulb was examined in\n                      <jats:italic>Snca<\/jats:italic>\n                      knockout mice. \u03b1\u2010Synuclein pathology and neurodegeneration were evaluated in PFF\u2010injected A53T BAC\u2010\n                      <jats:italic>SNCA<\/jats:italic>\n                      transgenic mice with perampanel or vehicle treatment for 2 and 9\u2009months after the removal of injected PFFs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Neuronal uptake of PFFs was blocked by a dynamin inhibitor but not by a clathrin inhibitor in vitro. Oral administration of perampanel significantly increased the level of phosphorylated dynamin1 in mouse brains, suggesting that perampanel suppresses dynamin\u2010dependent endocytosis in vivo. PFFs injected into the olfactory bulb disappeared within 1\u2009week. In A53T BAC\u2010\n                      <jats:italic>SNCA<\/jats:italic>\n                      transgenic mice injected with PFFs, perampanel treatment starting 1\u2009week after PFFs injection reduced the amount of \u03b1\u2010synuclein pathology in second\u2010 or higher\u2010order regions, but not in first\u2010order regions, from the injection site and ameliorated neurodegeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Perampanel could be a disease\u2010modifying drug for Lewy body disease that modulates transsynaptic \u03b1\u2010synuclein propagation, presumably by suppressing dynamin\u2010dependent endocytosis. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70191","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T07:26:28Z","timestamp":1767943588000},"page":"1183-1196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perampanel Blocks Transsynaptic \u03b1\u2010Synuclein Propagation and Neurodegeneration in a Mouse Model of Lewy Body Disease"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-7923","authenticated-orcid":false,"given":"Jun","family":"Ueda","sequence":"first","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine  Kyoto 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