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Although 10%\u201315% of PD cases are due to familial mutations, the remaining cases are sporadic, often linked to various factors, like pesticides and metals. For example, rotenone and dopamine are known to be involved in PD pathology and are suggested to cause changes in \u03b1\u2010Syn protein homeostasis, although the mechanism by which they influence \u03b1\u2010Syn and cellular toxicity is largely unknown. In this work, we demonstrate that both dopamine and rotenone promote the LLPS of \u03b1\u2010Syn. Although rotenone promotes the liquid\u2010to\u2010solid transition almost instantaneously, dopamine, however, maintains a liquid state for a long time and rather delays the solidification process, unlike \u03b1\u2010Syn alone. Similarly, exposure to both toxicants resulted in faster LLPS in SH\u2010SY5Y cells. Interestingly, irrespective of their impact on material properties, rotenone promotes the faster formation of oligomers and amyloid fibrils, while dopamine exhibits oligomer formation and delayed fibrillation, both of which result in higher cytotoxicity. Our results provide new insight into the molecular processes underlying PD by indicating that endogenous dopamine stress and environmental toxicants converge on phase\u2010separation dynamics as a common mechanism of \u03b1\u2010Syn pathology.<\/jats:p>","DOI":"10.1002\/smll.202514922","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:46:07Z","timestamp":1773305167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dopamine and Rotenone Modulate \u03b1\u2010Synuclein Phase Separation and Liquid to Solid Transition"],"prefix":"10.1002","volume":"22","author":[{"given":"Riya","family":"Bera","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering IIT Bombay  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouvik","family":"Manna","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering IIT Bombay  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering IIT Bombay  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering IIT Bombay  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-1565","authenticated-orcid":false,"given":"Samir K.","family":"Maji","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering IIT Bombay  Mumbai India"},{"name":"Sunita Sanghi Centre of Aging and Neurodegenerative Diseases IIT Bombay  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"M. 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