Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Mice.

ABSTRACT:

Background

Accumulation of hyperphosphorylated tau (pTau) protein is associated with synaptic dysfunction in Alzheimer's disease (AD). We previously demonstrated that neuroprotection in familial mouse models of AD could be achieved by targeting mitochondria complex I (MCI) and activating the adaptive stress response. Efficacy of this strategy on pTau-related pathology remained unknown.

Objective

To investigate the effect of specific MCI inhibitor tricyclic pyrone compound CP2 on levels of human pTau, memory function, long term potentiation (LTP), and energy homeostasis in 18-month-old 3xTg-AD mice and explore the potential mechanisms.

Methods

CP2 was administered to male and female 3xTg-AD mice from 3.5-18 months of age. Cognitive function was assessed using the Morri

SUBMITTER: Stojakovic A 

PROVIDER: S-EPMC7902954 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature