Impaired mitochondrial calcium efflux contributes to disease progression in models of Alzheimer's disease.

ABSTRACT: Impairments in neuronal intracellular calcium (_iCa²⁺) handling may contribute to Alzheimer's disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD progression, and mitochondrial calcium (_mCa²⁺) signaling is a key regulator of both of these processes. Here, we report remodeling of the _mCa²⁺ exchange machinery in the prefrontal cortex of individuals with AD. In the 3xTg-AD mouse model impaired _mCa²⁺ efflux capacity precedes neuropathology. Neuronal deletion of the mitochondrial Na⁺/Ca²⁺ exchanger (NCLX, Slc8b1 gene) accelerated memory decline and increased amyloidosis and tau pathology. Further, genetic rescue of neuronal NCLX in 3xTg-AD

SUBMITTER: Jadiya P 

PROVIDER: S-EPMC6715724 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature