Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration

Sant'Anna, Ricardo, Navarro, Susanna, Ventura, Salvador, Paraoan, Luminita ORCID: 0000-0001-7568-7116 and Foguel, Debora (2016) Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration. FEBS LETTERS, 590 (5). pp. 644-654.

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Abstract

Variant B (VB) of cystatin C has a mutation in its signal peptide (A25T), which interferes with its processing leading to reduced secretion and partial retention in the vicinity of the mitochondria. There are genetic evidences of the association of VB with Alzheimer's disease (AD) and age-related macular degeneration (AMD). Here, we investigated aggregation and amyloid propensities of unprocessed VB combining computational and in vitro studies. Aggregation predictors revealed the presence of four aggregation-prone regions, with a strong one at the level of the signal peptide, which indeed formed toxic aggregates and mature amyloid fibrils in solution. In light of these results, we propose for the first time the role of the signal peptide in pathogenesis of AD and AMD.

Item Type:	Article
Uncontrolled Keywords:	Alzheimers' disease and exudative age-related macular degeneration, human cystatin C, protein aggregation
Depositing User:	Symplectic Admin
Date Deposited:	04 Jul 2016 08:24
Last Modified:	19 Jan 2023 07:35
DOI:	10.1002/1873-3468.12093
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3001790