Identifying compounds that enhance the resilience of isolated neuronal mitochondria against dysfunction induced by Aß42 and tau oligomers

Abstract

The oligomeric intraneuronal accumulation of amyloid beta AB42 (AB42 ) and Tau has been directly linked to Alzheimer's Disease (AD) pathology and progression. In particular, mounting evidence indicates that oligomer-induced mitochondrial abnormalities are early occurrences, preceding neurological pathology and clinical symptoms characteristic of AD. Perforation of mitochondrial membranes leads to the release of pro-apoptotic proteins such as cytochrome c into the cellular cytosol, triggering neuronal apoptosis. The main aims of the study were to determine any effects of Ab42 and Tau aggregates on mitochondrial membranes and subsequently identify mitochondrial-protective compounds. The rationale behind the study was to gain further insight as to the mechanisms involved in AbTau induced mito-toxicity, and identify potential candidates for effective mitochondrial drugs in AD.