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α-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila

Lookup NU author(s): Professor Tiago OuteiroORCiD


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© The Author 2014. Protein misfolding and aggregation is a major hallmark of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Until recently, the consensus was that each aggregation-prone protein was characteristic of each disorder [α-synuclein (α-syn)/PD, mutant huntingtin (Htt)/HD, Tau and amyloid beta peptide/AD]. However, growing evidence indicates that aggregation-prone proteins can actually co-aggregate and modify each other's behavior and toxicity, suggesting that this process may also contribute to the overlap in clinical symptoms across different diseases. Here, we show that α-syn and mutant Htt co-aggregate in vivo when co-expressed in Drosophila and produce a synergistic age-dependent increase in neurotoxicity associated to a decline in motor function and life span. Altogether, our results suggest that the co-existence of α-syn and Htt in the same neuronal cells worsens aggregation-related neuropathologies and accelerates disease progression.

Publication metadata

Author(s): Pocas GM, Branco-Santos J, Herrera F, Outeiro TF, Domingos PM

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2014

Volume: 24

Issue: 7

Pages: 1898-1907

Print publication date: 01/04/2015

Online publication date: 01/12/2014

Acceptance date: 27/11/2014

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/ddu606

PubMed id: 25452431


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