PROTEIN FOLDING

Interfering in an aggregation pathway

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Science  17 Apr 2015:
Vol. 348, Issue 6232, pp. 299
DOI: 10.1126/science.348.6232.299-b

Most dementia cases are caused by neurodegenerative Alzheimer's disease. Plaques composed of fibrils of a 42-residue amyloid-β peptide (Aβ42) are characteristic of this disease. There is evidence that neurotoxicity is caused by Aβ42 oligomers rather than the fibrils, but fibrils catalyze the formation of oligomers. Cohen et al. show that the human chaperone domain Briochos binds to the surface of Aβ42 fibrils and prevents them from catalyzing oligomer formation. In electrophysiology experiments in mouse brain slices, Briochos prevented the inhibition of neural oscillations caused by Aβ42 aggregation. In this case, a chaperone acts not by promoting folding or preventing misfolding but by targeting a nucleation step in the aggregation pathway.

Nat. Struct. Mol. Biol. 10.1038/nsmb.2971 (2015).

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