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We recently showed that glycation of aSyn by methylglyoxal (MGO) potentiates its oligomerization and toxicity, induces dopaminergic neuronal cell loss in mice, and affects motor performance in flies. Small heat\u2010shock proteins (sHsps) are molecular chaperones that facilitate the folding of proteins or target misfolded proteins for clearance. Importantly, sHsps were shown to prevent aSyn aggregation and cytotoxicity. Upon treating cells with increasing amounts of methylglyoxal, we found that the levels of Hsp27 decreased in a dose\u2010dependent manner. Therefore, we hypothesized that restoring the levels of Hsp27 in glycating environments could alleviate the pathogenicity of aSyn. Consistently, we found that Hsp27 reduced MGO\u2010induced aSyn aggregation in cells, leading to the formation of nontoxic aSyn species. Remarkably, increasing the levels of Hsp27 suppressed the deleterious effects induced by MGO. Our findings suggest that in glycating environments, the levels of Hsp27 are important for modulating the glycation\u2010associated cellular pathologies in synucleinopathies.<\/jats:p>","DOI":"10.1096\/fj.201902936r","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T13:09:55Z","timestamp":1586264995000},"page":"6718-6728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hsp27 reduces glycation\u2010induced toxicity and aggregation of alpha\u2010synuclein"],"prefix":"10.1096","volume":"34","author":[{"given":"Hugo","family":"Vicente Miranda","sequence":"first","affiliation":[{"name":"CEDOC, Chronic Diseases Research Center NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas Universidade Nova de Lisboa Lisboa Portugal"}]},{"given":"Ana","family":"Cheg\u00e3o","sequence":"additional","affiliation":[{"name":"CEDOC, Chronic Diseases Research Center NOVA Medical School, 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