作者
Hugo Vicente Miranda, Éva M Szegő, Luís Oliveira, Carlo Breda, Ekrem Darendelioglu, Rita M de Oliveira, Diana G Ferreira, Marcos A Gomes, Ruth Rott, Márcia Oliveira, Francesca Munari, Francisco J Enguita, Tânia Simões, Eva F Rodrigues, Michael Heinrich, Ivo C Martins, Irina Zamolo, Olaf Riess, Carlos Cordeiro, Ana Ponces-Freire, Hilal A Lashuel, Nuno C Santos, Luisa V Lopes, Wei Xiang, Thomas M Jovin, Deborah Penque, Simone Engelender, Markus Zweckstetter, Jochen Klucken, Flaviano Giorgini, Alexandre Quintas, Tiago F Outeiro
发表日期
2017/5/1
期刊
Brain
卷号
140
期号
5
页码范围
1399-1419
出版商
Oxford University Press
简介
α-Synuclein misfolding and aggregation is a hallmark in Parkinson’s disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-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 α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α …
学术搜索中的文章
H Vicente Miranda, ÉM Szegő, LMA Oliveira, C Breda… - Brain, 2017