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bioRxiv · 10.1101/2021.04.02.438207

Clusterin in Alzheimer's disease: an amyloidogenic inhibitor of amyloid formation

Spatharas, P. M.·Nasi, G. I.·Tsiolaki, P. L.·Trougakos, I. P.·Iconomidou, V. A.
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Abstract

Clusterin is a heterodimeric glycoprotein (- and {beta}-chain), which has been described as an extracellular molecular chaperone. In humans, clusterin is an amyloid associated protein, co-localizing with fibrillar deposits in several amyloidoses, including Alzheimers disease. To clarify its potential implication in amyloid formation, we located aggregation-prone regions within the sequence of clusterin -chain, via computational methods. We had peptide-analogues of each region chemically synthesized and experimentally demonstrated that all of them can form amyloid-like fibrils. We also provide evidence that the same peptide-analogues can inhibit amyloid-{beta} fibril formation. These findings elucidate parts of the molecular mechanism in which clusterin inhibits amyloid formation. At the same time, they hint that molecular chaperones with amyloidogenic properties might have a role in the regulation of amyloid formation, essentially acting as functional amyloids.

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Spatharas, P. M., Nasi, G. I., Tsiolaki, P. L., Trougakos, I. P., Iconomidou, V. A.. 2021-04-04. Clusterin in Alzheimer's disease: an amyloidogenic inhibitor of amyloid formation. https://doi.org/10.1101/2021.04.02.438207

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