{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:52:38Z","timestamp":1787496758865,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T00:00:00Z","timestamp":1545264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["09\/263\/0961"],"award-info":[{"award-number":["09\/263\/0961"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oligomerization of \u03b3\u2010Synuclein is known to have implications for both neurodegeneration and cancer. Although it is known to co\u2010exist with the fibrillar deposits of \u03b1\u2010Synuclein (Lewy bodies), a hallmark in Parkinson's disease (PD), the effect of potential therapeutic modulators on the fibrillation pathway of \u03b3\u2010Syn remains unexplored. By a combined use of various biophysical tools and cytotoxicity assays we demonstrate that the flavonoid epigallocatechin\u20103\u2010gallate (EGCG) significantly suppresses \u03b3\u2010Syn fibrillation by affecting its nucleation and binds with the unstructured, nucleus forming oligomers of \u03b3\u2010Syn to modulate the pathway to form \u03b1\u2010helical containing higher\u2010order oligomers (~158 kDa and ~ 670 kDa) that are SDS\u2010resistant and conformationally restrained in nature. Seeding studies reveal that these oligomers although \u201con\u2010pathway\u201d in nature, are kinetically retarded and rate\u2010limiting species that slows down fibril elongation. We observe that EGCG also disaggregates the protofibrils and mature \u03b3\u2010Syn fibrils into similar SDS\u2010resistant oligomers. Steady\u2010state and time\u2010resolved fluorescence spectroscopy and isothermal titration calorimetry (ITC) reveal a weak non\u2010covalent interaction between EGCG and \u03b3\u2010Syn with the dissociation constant in the m\n                    <jats:italic>M<\/jats:italic>\n                    range (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    ~ 2\u201310 m\n                    <jats:italic>M<\/jats:italic>\n                    ). Interestingly, while EGCG\u2010generated oligomers completely rescue the breast cancer (MCF\u20107) cells from \u03b3\u2010Syn toxicity, it reduces the viability of neuroblastoma (SH\u2010SY5Y) cells. However, the disaggregated oligomers of \u03b3\u2010Syn are more toxic than the disaggregated fibrils for MCF\u20107cells. These findings throw light on EGCG\u2010mediated modulation of \u03b3\u2010Syn fibrillation and suggest that investigation on the effects of such modulators on \u03b3\u2010Syn fibrillation is critical in identifying effective therapeutic strategies using small molecule modulators of synucleopathies.\n                  <\/jats:p>","DOI":"10.1002\/pro.3549","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T06:48:52Z","timestamp":1541400532000},"page":"382-402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Suppression, disaggregation, and modulation of \u03b3\u2010Synuclein fibrillation pathway by green tea polyphenol EGCG"],"prefix":"10.1002","volume":"28","author":[{"given":"Sneha","family":"Roy","sequence":"first","affiliation":[{"name":"Biophysical Chemistry Laboratory, School of Biotechnology Jawaharlal Nehru University New Mehrauli Road, New Delhi, 110067 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