PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy.

ABSTRACT: As a primary cause of dementia and death in older people, Alzheimer's disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement

SUBMITTER: Jiang XJ 

PROVIDER: S-EPMC8763800 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature