Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation.

ABSTRACT: Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca²⁺ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca²⁺ levels followed by a later Ca²⁺ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro, and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca²⁺ CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis el

SUBMITTER: Betzer C 

PROVIDER: S-EPMC5934765 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature