Abstract:
:Nine human neurodegenerative diseases are due to expansion of a CAG repeat- encoding glutamine within the open reading frame of the respective genes. Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell death during development. To address whether miRNA pathways play a role in neurodegeneration, we tested whether genes critical for miRNA processing modulated toxicity induced by the spinocerebellar ataxia type 3 (SCA3) protein. These studies revealed a striking enhancement of polyQ toxicity upon reduction of miRNA processing in Drosophila and human cells. In parallel genetic screens, we identified the miRNA bantam (ban) as a potent modulator of both polyQ and tau toxicity in flies. Our studies suggest that ban functions downstream of toxicity of the SCA3 protein, to prevent degeneration. These findings indicate that miRNA pathways dramatically modulate polyQ- and tau-induced neurodegeneration, providing the foundation for new insight into therapeutics.
journal_name
Mol Celljournal_title
Molecular cellauthors
Bilen J,Liu N,Burnett BG,Pittman RN,Bonini NMdoi
10.1016/j.molcel.2006.07.030subject
Has Abstractpub_date
2006-10-06 00:00:00pages
157-63issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(06)00532-6journal_volume
24pub_type
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