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Drosophila Histone Deacetylase 6 Protects Dopaminergic Neurons against α-Synuclein Toxicity by Promoting Inclusion Formation
Parkinson's disease (PD) is associated with progressive degeneration of dopaminergic (DA) neurons. We report for the first time that the Drosophila histone deacetylase 6 (dHDAC6) plays a critical role in the protection of DA neurons and the formation of α-synuclein inclusions by using a Drosoph...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893978/ https://www.ncbi.nlm.nih.gov/pubmed/20444973 http://dx.doi.org/10.1091/mbc.E10-03-0200 |
Sumario: | Parkinson's disease (PD) is associated with progressive degeneration of dopaminergic (DA) neurons. We report for the first time that the Drosophila histone deacetylase 6 (dHDAC6) plays a critical role in the protection of DA neurons and the formation of α-synuclein inclusions by using a Drosophila PD model constructed by ectopic expression of human α-synuclein. Depletion of dHDAC6 significantly enhances the effects caused by ectopic expression of α-synuclein, namely, loss of DA neurons, retinal degeneration, and locomotor dysfunction. Expression of α-synuclein in the DA neurons leads to fewer inclusions in the brains of dHDAC6 mutant flies than in wild-type flies. Conversely, overexpression of dHDAC6 is able to suppress the α-synuclein–induced DA neuron loss and retinal degeneration and promote inclusion formation. Furthermore, mutation of dHDAC6 reinforces the accumulation of oligomers that are suggested to be a toxic form of α-synuclein. We propose that α-synuclein inclusion formation in the presence of dHDAC6 protects DA neurons from being damaged by oligomers, which may uncover a common mechanism for synucleinopathies. |
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