In:
FEBS Letters, Wiley, Vol. 590, No. 5 ( 2016-03), p. 644-654
Kurzfassung:
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 .
Materialart:
Online-Ressource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1002/1873-3468.12093
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2016
ZDB Id:
1460391-3
SSG:
12
