{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:14:05Z","timestamp":1780582445870,"version":"3.54.1"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22ym0126095h0001"],"award-info":[{"award-number":["22ym0126095h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06644"],"award-info":[{"award-number":["22K06644"]}],"id":[{"id":"10.13039\/501100001691","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":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>We previously found that a decoy peptide derived from the C\u2010terminal sequence of \u03b1\u2010Synuclein (\u03b1Syn) prevents cytotoxic \u03b1Syn aggregation caused by fatty acid\u2010binding protein 3 (FABP3) in vitro. In this study, we continued to utilize \u03b1Syn\u2010derived peptides to further validate their effects on \u03b1Syn neurotoxicity and behavioral impairments in \u03b1Syn preformed fibrils (PFFs)\u2010injected mouse model of Parkinson's disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were injected with \u03b1Syn PFFs in the bilateral olfactory bulb (OB) and then were subjected to behavioral analysis at 2\u2010week intervals post\u2010injection. Peptides nasal administration was initiated one week after injection. Changes in phosphorylation of \u03b1Syn and neuronal damage in the OB were measured using immunostaining at week 4. The effect of peptides on the interaction between \u03b1Syn and FABP3 was examined using co\u2010immunoprecipitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u03b1Syn PFF\u2010injected mice showed significant memory loss but no motor function impairment. Long\u2010term nasal treatment with peptides effectively prevented memory impairment. In peptide\u2010treated \u03b1Syn PFF\u2010injected mice, the peptides entered the OB smoothly through the nasal cavity and were mainly concentrated in neurons in the mitral cell layer, significantly suppressing the excessive phosphorylation of \u03b1Syn and reducing the formation of \u03b1Syn\u2010FABP3 oligomers, thereby preventing neuronal death. The addition of peptides also blocked the interaction of \u03b1Syn and FABP3 at the recombinant protein level, and its effect was strongest at molar concentrations comparable to those of \u03b1Syn and FABP3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that the \u03b1Syn decoy peptide represents a novel therapeutic approach for reducing the accumulation of toxic \u03b1Syn\u2010FABP3 oligomers in the brain, thereby preventing the progression of synucleinopathies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14120","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T09:34:14Z","timestamp":1676367254000},"page":"1547-1560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u03b1\u2010Synuclein decoy peptide protects mice against \u03b1\u2010synuclein\u2010induced memory 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