Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer's disease as a mitophagy receptor.

ABSTRACT: Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We show levels of Disrupted-in-schizophrenia-1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ-treated cultured cells. Disrupted-in-schizophrenia-1 contains a canonical LC3-interacting region (LIR) motif (²¹⁰ FSFI²¹³ ), through which DISC1 directly binds to LC3-I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking-down of DISC1 blocks Aβ-induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which aboli

SUBMITTER: Wang ZT 

PROVIDER: S-EPMC6351828 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature