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Although aminochrome-induced oxidative stress and its inhibitory effects on microtubule polymerization are well documented, its impact on protein aggregation remains poorly understood. The aim of this research was to evaluate the effects of aminochrome on protein aggregate accumulation in SH-SY5Y cells differentiated into dopaminergic neurons. While the role of aminochrome in autophagy has been described, its direct effect on autophagosome\u2013lysosome fusion has not been studied. Our findings reveal that aminochrome, like vinblastine, delays autophagosome\u2013lysosome fusion and induces cell death. This inhibitory effect was also observed in the presence of autophagy inducers, which partially attenuated aminochrome-induced cell death. Under these conditions of disruptions in autophagosome\u2013lysosome fusion, a marked accumulation of perinuclear vimentin and ubiquitin aggregates was observed. Aminochrome also increased colocalization between vimentin and ubiquitin. Interestingly, ubiquitin aggregates were also detected within the nucleus. These findings suggest that aminochrome-induced disruption of the microtubule network, particularly its impairment of autophagosome\u2013lysosome fusion and promotion of protein aggregation, may represent a critical mechanism leading to cell death. In addition, inhibition of autophagosome\u2013lysosome fusion may contribute to the accumulation of perinuclear and nuclear protein aggregates, which may be associated with either toxic or non-toxic pathways. Our findings underscore the therapeutic potential of targeting both microtubule stabilization and proteostasis pathways, including autophagy and the ubiquitin\u2013proteasome system (UPS), in Parkinson\u2019s disease, highlighting the need for further research into nuclear proteotoxicity mechanisms.<\/jats:p>","DOI":"10.3390\/antiox15060739","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:50:58Z","timestamp":1781157058000},"page":"739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aminochrome-Induced Disruption of Autophagosome-Lysosome Fusion: Implications for Protein Aggregation in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Andrea","family":"Brice\u00f1o","sequence":"first","affiliation":[{"name":"Molecular and Clinical Pharmacology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Faculty of Medicine, University of Chile, Independencia 1027, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cipriano","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Pallac\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Salinas","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8774","authenticated-orcid":false,"given":"Carola","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Facultad Artes Liberales, Universidad Adolfo Ib\u00e1\u00f1ez, Vi\u00f1a del Mar 2580335, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-368X","authenticated-orcid":false,"given":"Juan F.","family":"Vivanco","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda y Ciencias, Universidad Adolfo Ib\u00e1\u00f1ez, Vi\u00f1a del Mar 2580335, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Caro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-673X","authenticated-orcid":false,"given":"Juan","family":"Segura-Aguilar","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Faculty of Medicine, University of Chile, Independencia 1027, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-7513","authenticated-orcid":false,"given":"Irmgard B.","family":"Paris","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Austral Biotech, Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tom\u00e1s, Vi\u00f1a del Mar 2561780, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s12035-012-8280-y","article-title":"The Lewy body in Parkinson\u2019s disease and related neurodegenerative disorders","volume":"47","author":"Wakabayashi","year":"2013","journal-title":"Mol. 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