NYU Chemistry Professor (and University President) Andrew Hamilton and postdoctoral fellow Sunil Kumar (currently Assistant Professor of Chemistry at the University of Denver) published research with colleagues from the University of Stockholm and from NYU Abu Dhabi in Cell Reports, Physical Science. The article, entitled, "Designed Cell-Penetrating Peptide Inhibitors of Amyloid-beta Aggregation and Cytotoxicity" was picked up by NYU Research Highlights, describing how protein-based therapeutics prevent protein aggregation associated with Alzheimer’s and other neurodegenerative diseases.
Summary: Amyloid proteins and peptides are a major contributing factor to the development of various neurodegenerative disorders, including Alzheimer’s and prion diseases. Previously, a designed cell-penetrating peptide (CPP) comprising a hydrophobic signal sequence followed by a prion protein (PrP)-derived polycationic sequence (PrP23–28: KKRPKP) was shown to have potent anti-prion properties. Here, we extend this approach toward the amyloid-beta (Aβ) peptide amyloid formation, which is associated with Alzheimer’s disease. We characterized the interactions of the CPP with Aβ using complementary in vitro and in silico experiments. We report that the CPP stabilizes Aβ in a non-amyloid state and inhibits Aβ-induced neurotoxicity. Moreover, replacing PrP23–28 with a corresponding segment from Aβ results in a construct with similar CPP functionality and antagonism of Aβ aggregation and neurotoxicity. Our findings reveal a general underlying principle for inhibition of pathogenic protein aggregation that may facilitate the design of CPP-based therapeutics for amyloid diseases.
This research was widely picked up by the international press as follows:
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Al Shabiba
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