TY - JOUR
T1 - α-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila
AU - Poças, Gonçalo M.
AU - Branco-Santos, Joana
AU - Herrera, Federico
AU - Outeiro, Tiago Fleming
AU - Domingos, Pedro M.
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84926456769&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu606
DO - 10.1093/hmg/ddu606
M3 - Article
AN - SCOPUS:84926456769
VL - 24
SP - 1898
EP - 1907
JO - Human molecular genetics
JF - Human molecular genetics
SN - 0964-6906
IS - 7
M1 - ddu606
ER -