Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.

The conversion of native peptides and proteins into amyloid aggregates is a hallmark of over 50 human disorders, including Alzheimer's and Parkinson's diseases. Increasing evidence implicates misfolded protein oligomers produced during the amyloid formation process as the primary cytotoxic agents in many of these devastating conditions. In this review, we analyze the processes by which oligomers are formed, their structures, physicochemical properties, population dynamics, and the mechanisms of their cytotoxicity. We then focus on drug discovery strategies that target the formation of oligomers and their ability to disrupt cell physiology and trigger degenerative processes. © 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Citation

Dillon J Rinauro, Fabrizio Chiti, Michele Vendruscolo, Ryan Limbocker. Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases. Molecular neurodegeneration. 2024 Feb 20;19(1):20

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PMID: 38378578

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