Carboxyl truncation of α-synuclein occurs early and is influenced by human APOE genotype in transgenic mouse models of α-synuclein pathogenesis.

ABSTRACT: Post-translational modifications to the carboxyl (C) terminus domain of α-synuclein can play an important role in promoting the pathologic aggregation of α-synuclein. Various cleavages that diminish this highly charged, proline-rich region can result in exposure of hydrophobic, aggregation-prone regions, thereby accelerating the aggregation kinetics of α-synuclein into misfolded, pathologic forms. C-terminally truncated forms of α-synuclein are abundant in human diseased brains compared to controls, suggesting a role in disease pathogenesis. Factors that alter the homeostatic proteolytic processing of α-synuclein may ultimately tip the balance towards a progressive disease state. Apolipoprotein E (APOE) has been implicated in the acceleration of cognitive impairment in patients with Lewy b

SUBMITTER: Lloyd GM 

PROVIDER: S-EPMC10363304 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature