MicroRNA pathways modulate polyglutamine-induced neurodegeneration.

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 Cell

journal_title

Molecular cell

authors

Bilen J,Liu N,Burnett BG,Pittman RN,Bonini NM

doi

10.1016/j.molcel.2006.07.030

subject

Has Abstract

pub_date

2006-10-06 00:00:00

pages

157-63

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(06)00532-6

journal_volume

24

pub_type

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