The polyQ diet

How polyQ tracts block autophagy in neurodegenerative diseases

Expanded polyglutamine repeats at the ends of disease-causing proteins are well known to promote formation of aggregates that drive various neurodegenerative disorders. A new study from the University of Cambridge shows those repeats have a second pathological role -- preventing elimination of the aggregates by blocking autophagy.

The results reinforce the emerging notion that boosting autophagy could be a general strategy for combating neurodegenerative diseases involving aggregated proteins.

Despite a moniker that implies self-destruction, autophagy is a survival mechanism induced by cellular stress in which specialized organelles called autophagosomes gobble up old proteins and organelles and deliver them to lysosomes for degradation.

Autophagy is a growing target for drug developers because it is also a clearance system for misfolded and aggregated proteins that cause disease, and subsets of patients with Parkinson's disease and amyotrophic lateral sclerosis (ALS) harbor mutations in components of the pathway.

Neurodegenerative diseases such as Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3) involve polyglutamine (polyQ) expansions, in which extra glutamines at the end of mutant proteins

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