Proteasome Activation to Combat Proteotoxicity
Department of Chemistry; Michigan State University, East Lansing, MI 48824, USA
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Author to whom correspondence should be addressed.
Academic Editor: Steven Verhelst
Molecules 2019, 24(15), 2841; https://doi.org/10.3390/molecules24152841
Received: 24 June 2019
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Revised: 22 July 2019
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Accepted: 1 August 2019
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Published: 5 August 2019
(This article belongs to the Special Issue Proteasome Regulators: Activators and Inhibitors)
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.
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Keywords:
proteasome; activation; enhancement; intrinsically disordered proteins; IDP; neurodegenerative disease; proteotoxic; oxidative damage; aggregates
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MDPI and ACS Style
Jones, C.L.; Tepe, J.J. Proteasome Activation to Combat Proteotoxicity. Molecules 2019, 24, 2841. https://doi.org/10.3390/molecules24152841
AMA Style
Jones CL, Tepe JJ. Proteasome Activation to Combat Proteotoxicity. Molecules. 2019; 24(15):2841. https://doi.org/10.3390/molecules24152841
Chicago/Turabian StyleJones, Corey L., and Jetze J. Tepe. 2019. "Proteasome Activation to Combat Proteotoxicity" Molecules 24, no. 15: 2841. https://doi.org/10.3390/molecules24152841
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