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Inhibition of amyloid fibrillogenesis and toxicity by a peptide chaperone

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Abstract

Aggregation of proteins in tissues is associated with several diseases, including Alzheimer's disease. It is characterized by the accumulation of amyloid β peptide (Aβ) in the extracellular spaces of the brain cells, resulting in neuronal death and other pathological changes. α-Crystallin, a small heat-shock protein in lens, and a peptide chaperone having the functional site sequence DFVIFLDVKHFSPEDLTVK of αA-crystallin may inhibit Aβ fibrillogenesis and toxicity. The peptide chaperone (mini-αA-crystallin), having an Aβ interacting domain and a complex solubilizing domain, was shown in previous studies to prevent aggregation of several proteins under denaturing conditions. In this in vitro study, using transmission electron microscopy and thioflavin T binding assay, we show that mini-αA-crystallin arrests the fibril formation of Aβ peptides. Mini-αA-crystallin also suppresses the toxic action of Aβ on rat pheochromocytoma (PC12) cells. The wide chaperoning capability of the peptide and its ability to inhibit amyloid fibril formation and suppress toxicity suggest that mini-αA-crystallin may serve as a universal chaperone in controlling diseases of protein aggregation, including Alzheimer's disease. (Mol Cell Biochem 267: 147–155, 2004)

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  1. Departments of Ophthalmology and Biochemistry, University of Missouri, Columbia, MO, USA

    Puttur Santhoshkumar & Krishna K. Sharma

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  1. Puttur Santhoshkumar
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  2. Krishna K. Sharma
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Santhoshkumar, P., Sharma, K.K. Inhibition of amyloid fibrillogenesis and toxicity by a peptide chaperone. Mol Cell Biochem 267, 147–155 (2004). https://doi.org/10.1023/B:MCBI.0000049373.15558.b8

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