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dc.contributor.authorVicente Miranda, Hugo and Szego, Eva M. and Oliveira, Luis M. A. and Breda, Carlo and Darendelioglu, Ekrem and de Oliveira, Rita M. and Ferreira, Diana G. and Gomes, Marcos A. and Rott, Ruth and Oliveira, Marcia and Munari, Francesca and Enguita, Francisco J. and Simoes, Tania and Rodrigues, Eva F. and Heinrich, Michael and Martins, Ivo C. and Zamolo, Irina and Riess, Olaf and Cordeiro, Carlos and Ponces-Freire, Ana and Lashuel, Hilal A. and Santos, Nuno C. and Lopes, Luisa V. and Xiang, Wei and Jovin, Thomas M. and Penque, Deborah and Engelender, Simone and Zweckstetter, Markus and Klucken, Jochen and Giorgini, Flaviano and Quintas, Alexandre and Outeiro, Tiago F.
dc.date.accessioned2021-04-02T12:03:31Z
dc.date.available2021-04-02T12:03:31Z
dc.date.issued2017
dc.identifier10.1093/brain/awx056
dc.identifier.issn0006-8950
dc.identifier.urihttp://acikerisim.bingol.edu.tr/handle/20.500.12898/2495
dc.description.abstractalpha-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of alpha-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced alpha-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of alpha-synuclein, reducing membrane binding, impaired the clearance of alpha-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of alpha-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.
dc.language.isoEnglish
dc.sourceBRAIN
dc.titleGlycation potentiates alpha-synuclein-associated neurodegeneration in synucleinopathies
dc.typeArticle


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