Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 1, Pages 41-52Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202007924
Keywords
amyloid; chaperone; conformational disease; misfolding; nanoparticle
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Funding
- Spanish Ministerio de Ciencia, Innovacin y Universidades [RED2018-102471-T, CTQ2017-88446-R]
- NIH [P41-GM103311]
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The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, primarily neurodegenerative diseases. Recent findings suggest that impairment in proteostasis network may lead to accumulation and spread of amyloids, contributing to a new focus in anti-amyloid drug design. Chaperones, as known regulators of proteostasis, represent interesting targets for the development of novel therapeutics, with the concept of nanochaperone potentially leading towards the development of cost-effective, disease-modifying drugs.
The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, including primarily neurodegenerative diseases. Such disorders are characterized by misfolded proteins that lose their normal physiological roles and acquire toxicity. Recent findings suggest that proteostasis network impairment may be one of the causes leading to the accumulation and spread of amyloids. These observations are certainly contributing to a new focus in anti-amyloid drug design, whose efforts are so far being centered on single-target approaches aimed at inhibiting amyloid aggregation. Chaperones, known to maintain proteostasis, hence represent interesting targets for the development of novel therapeutics owing to their potential protective role against protein misfolding diseases. In this minireview, research on nanoparticles that can either emulate or help molecular chaperones in recognizing and/or correcting protein misfolding is discussed. The nascent concept of nanochaperone may indeed set future directions towards the development of cost-effective, disease-modifying drugs to treat several currently fatal disorders.
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