The role of mitochondrial impairment on Alzheimer ´s disease neurodegeneration: the Tau connection.

The role of mitochondrial impairment on Alzheimer´s disease neurodegeneration: the Tau connection. Curr Neuropharmacol. 2020 May 24;: Authors: Quntanilla RA, Tapia-Monsalves C Abstract Accumulative evidence has shown that mitochondrial dysfunction plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial impairment actively contributes to the synaptic and cognitive failure that characterizes AD. The presence of soluble pathological forms of tau like hyperphosphorylated at Ser396 and Ser404 and cleaved at Asp421 by caspase 3, negatively impacts mitochondrial bioenergetics, transport, and morphology in neurons. These adverse effects against mitochondria health will contribute to the synaptic impairment and cognitive decline showed in AD. Current studies suggest that mitochondrial failure induced by pathological tau forms are likely the result of the opening of the mitochondrial permeability transition pore (mPTP). mPTP is a mitochondrial mega-channel that is activated by increases in calcium and is associated with mitochondrial stress and apoptosis. This structure is composed of different proteins, where CypD is considered to be the primary mediator of mPTP activation. Also, new studies suggest that mPTP contributes to A pathology and oxidative stress in AD. Further, inhibition of mPTP through the reduction of CypD expression prevents cognitive and synaptic impairment in AD mouse models. More importantly, ...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research