Proteasome Activation to Combat Proteotoxicity.

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ID: 13059
2019
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Abstract
Loss of proteome fidelity leads to the accumulation of non-native protein aggregates and oxidatively damaged species: hallmarks of an aged cell. These misfolded and aggregated species are often found, and suggested to be the culpable party, in numerous neurodegenerative diseases including Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Diseases (AD). Many strategies for therapeutic intervention in proteotoxic pathologies have been put forth; one of the most promising is bolstering the efficacy of the proteasome to restore normal proteostasis. This strategy is ideal as monomeric precursors and oxidatively damaged proteins, so called "intrinsically disordered proteins" (IDPs), are targeted by the proteasome. This review will provide an overview of disorders in proteins, both intrinsic and acquired, with a focus on susceptibility to proteasomal degradation. We will then examine the proteasome with emphasis on newly published structural data and summarize current known small molecule proteasome activators.
Reference Key
jones2019proteasomemolecules Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jones, Corey L;Tepe, Jetze J;
Journal molecules
Year 2019
DOI
E2841
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Keywords Keywords not found

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