{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:31:30Z","timestamp":1781177490617,"version":"3.54.1"},"reference-count":77,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar Biomedical Research Institute","award":["Start-up Fund SF 2017-007"],"award-info":[{"award-number":["Start-up Fund SF 2017-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The accumulation and aggregation of \u03b1-synuclein (\u03b1-syn) is the main pathologic event in Parkinson\u2019s disease (PD), dementia with Lewy bodies, and multiple system atrophy. \u03b1-Syn-seeded fibril formation and its induced toxicity occupy a major role in PD pathogenesis. Thus, assessing compounds that inhibit this seeding process is considered a key towards the therapeutics of synucleinopathies. Using biophysical and biochemical techniques and seeding-dependent cell viability assays, we screened a total of nine natural compounds of alkaloid origin extracted from Chinese medicinal herbs. Of these compounds, synephrine, trigonelline, cytisine, harmine, koumine, peimisine, and hupehenine exhibited in vitro inhibition of \u03b1-syn-seeded fibril formation. Furthermore, using cell viability assays, six of these compounds inhibited \u03b1-syn-seeding-dependent toxicity. These six potent inhibitors of amyloid fibril formation and toxicity caused by the seeding process represent a promising therapeutic strategy for the treatment of PD and other synucleinopathies.<\/jats:p>","DOI":"10.3390\/molecules26123736","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T21:50:15Z","timestamp":1624225815000},"page":"3736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity"],"prefix":"10.3390","volume":"26","author":[{"given":"Simona S.","family":"Ghanem","sequence":"first","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0753-9944","authenticated-orcid":false,"given":"Hend S.","family":"Fayed","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"},{"name":"Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-5568","authenticated-orcid":false,"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-125X","authenticated-orcid":false,"given":"Jia-Hong","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant N.","family":"Vaikath","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janarthanan","family":"Ponraj","sequence":"additional","affiliation":[{"name":"Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Mansour","sequence":"additional","affiliation":[{"name":"Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar M. 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