α-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila
| Autor: | Federico Herrera, Joana Branco-Santos, Pedro Domingos, Tiago F. Outeiro, Gonçalo M. Poças |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
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Huntingtin Amyloid beta animal diseases Nerve Tissue Proteins Protein aggregation Animals Genetically Modified chemistry.chemical_compound Protein Aggregates Huntington's disease mental disorders Genetics medicine Huntingtin Protein Animals Humans Molecular Biology Genetics (clinical) Alpha-synuclein biology Neurodegeneration Neurotoxicity Neurodegenerative Diseases General Medicine Articles medicine.disease Cell biology nervous system diseases Disease Models Animal chemistry nervous system biology.protein alpha-Synuclein Drosophila Female |
| Popis: | © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 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. This work was supported by grant FCT-ANR/NEU-NMC/0006/2013 from Fundação para a Ciência e a Tecnologia, Portugal. G.M.P. was supported by a doctoral fellowship from the Fundação para a Ciência e a Tecnologia (SFRH/BD/61477/2009). J.B.S. and F.H. were supported by fellowships from the Fundação para a Ciência e a Tecnologia (SFRH/BD/85275/2012 and SFRH/BPD/63530/2009, respectively). F.H. and T.F.O. were also supported by seed funds from the European Huntington's Disease Network (EHDN). T.F.O. is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. |
| Databáze: | OpenAIRE |
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