{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:28:03Z","timestamp":1792441683256,"version":"4.5.0"},"reference-count":246,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Synucleinopathies are a group of neurodegenerative disorders caused by the accumulation of toxic species of \u03b1-synuclein. The common clinical features are chronic progressive decline of motor, cognitive, behavioral, and autonomic functions. They include Parkinson\u2019s disease, dementia with Lewy body, and multiple system atrophy. Their etiology has not been clarified and multiple pathogenic factors include oxidative stress, mitochondrial dysfunction, impaired protein degradation systems, and neuroinflammation. Current available therapy cannot prevent progressive neurodegeneration and \u201cdisease-modifying or neuroprotective\u201d therapy has been proposed. This paper presents the molecular mechanisms of neuroprotection by the inhibitors of type B monoamine oxidase, rasagiline and selegiline. They prevent mitochondrial apoptosis, induce anti-apoptotic Bcl-2 protein family, and pro-survival brain- and glial cell line-derived neurotrophic factors. They also prevent toxic oligomerization and aggregation of \u03b1-synuclein. Monoamine oxidase is involved in neurodegeneration and neuroprotection, independently of the catalytic activity. Type A monoamine oxidases mediates rasagiline-activated signaling pathways to induce neuroprotective genes in neuronal cells. Multi-targeting propargylamine derivatives have been developed for therapy in various neurodegenerative diseases. Preclinical studies have presented neuroprotection of rasagiline and selegiline, but beneficial effects have been scarcely presented. Strategy to improve clinical trials is discussed to achieve disease-modification in synucleinopathies.<\/jats:p>","DOI":"10.3390\/ijms231911059","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:47:06Z","timestamp":1663811226000},"page":"11059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Neuroprotective Function of Rasagiline and Selegiline, Inhibitors of Type B Monoamine Oxidase, and Role of Monoamine Oxidases in Synucleinopathies"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-1832","authenticated-orcid":false,"given":"Makoto","family":"Naoi","sequence":"first","affiliation":[{"name":"Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin 320-0195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakako","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin 320-0195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Shamoto-Nagai","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin 320-0195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00702-018-1920-2","article-title":"Special issue: Monoamine Oxidase A and B: Eternally Enigmatic Isoenzymes","volume":"125","author":"Shih","year":"2018","journal-title":"J. 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