Proteostasis Deficiencies

Publication Title: 
Nature Chemical Biology

In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread expression of the offending protein. PolyQ expansion may induce neurodegeneration by impairing proteostasis, but protein aggregation and toxicity tend to confound conventional measurements of protein stability. Here, we used optical pulse labeling to measure effects of polyQ expansions on the mean lifetime of a fragment of huntingtin, the protein that causes Huntington's disease, in living neurons.

Tsvetkov, Andrey S.
Arrasate, Montserrat
Barmada, Sami
Ando, D. Michael
Sharma, Punita
Shaby, Benjamin A.
Finkbeiner, Steven
Publication Title: 
Aging Cell

Nutrient availability influences an organism's life history with profound effects on metabolism and lifespan. The association between a healthy lifespan and metabolism is incompletely understood, but a central factor is glucose metabolism. Although glucose is an important cellular energy source, glucose restriction is associated with extended lifespan in simple animals and a reduced incidence of age-dependent pathologies in humans. We report here that glucose enrichment delays mutant polyglutamine, TDP-43, FUS, and amyloid-?

Tauffenberger, Arnaud
Vaccaro, Alexandra
Aulas, Anais
Vande Velde, Christine
Parker, J. Alex
Publication Title: 
Journal of Theoretical Biology

Mechanistic 'physics' models of protein folding fail to account for the observed spectrum and rate of protein folding and aggregation disorders in human populations, showing that more appropriately in vivo paradigms reflecting biological and other embedding contexts are needed for understanding the etiology, prevention, and treatment of these diseases. Here, a topological rate distortion analysis is applied to the problem that is analogous to Tlusty (2007) elegant exploration of the genetic code.

Wallace, Rodrick
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