Mitophagy alterations in Alzheimer's disease are associated with granulovacuolar degeneration and early tau pathology.

ABSTRACT:

Introduction

The cytoprotective PTEN-induced kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65-Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis.

Methods

Morphology, levels, and distribution of the mitophagy tag pS65-Ub were evaluated by biochemical analyses combined with tissue and single cell imaging in AD autopsy brain and in transgenic mouse models.

Results

Analyses revealed significant increases of pS65-Ub levels in AD brain, which strongly correlated with granulovacuolar degeneration (GVD) and early phospho

SUBMITTER: Hou X 

PROVIDER: S-EPMC8048674 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature