Current amyloid inhibitors: therapeutic applications and nanomaterial-based innovations.

Prog Neurobiol

Instituto Cajal, CSIC, Av. del Doctor Arce 37, Madrid 28002, Spain. Electronic address:

Published: February 2025

Amyloid proteins have long been in the spotlight for being involved in many degenerative diseases including Alzheimer´s, Parkinson´s or type 2 diabetes, which currently cannot be prevented and for which there is no effective treatment or cure. Here we provide a comprehensive review of inhibitors that act directly on the amyloidogenic pathway (at the monomer, oligomer or fibril level) of key pathological amyloids, focusing on the most representative amyloid-related diseases. We discuss the latest advancements in preclinical and clinical trials, focusing on cutting-edge developments, particularly on nanomaterials-based inhibitors, which offer unprecedented opportunities to address the complexity of protein misfolding disorders and are revolutionizing the landscape of anti-amyloid therapeutics. Notably, nanomaterials are impacting critical areas such as bioavailability, penetrability and functionality of compounds currently used in biomedicine, paving the way for more specific therapeutic solutions tailored to various amyloid-related diseases. Finally, we highlight the window of opportunity that comparative analysis with so-called functional amyloids opens for the development of innovative therapeutic approaches for these devastating diseases.

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http://dx.doi.org/10.1016/j.pneurobio.2025.102734DOI Listing

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