Research progress on the role of PGC1α in mitochondrial dysfunction associated with Alzheimer’s disease

Abstract

The transcriptional coactivator Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC1α) holds significant importance in the regulation of mitochondrial function during the pathogenesis of Alzheimer’s Disease (AD). PGC1α is highly expressed in the brain and has the ability to upregulate mitochondrial biogenesis. It modulates various metabolic pathways, such as the β-oxidation of fatty acids, which is important for generating ATP, and glycolysis, which supplies energy and protects against oxidative stress. The dysregulation of PGC1α can lead to alterations in energy metabolism in the brain, involving mitochondrial dysfunction and consequently decreasing cognitive function and neuronal pathologies. In the early stage of AD, the little amyloid-β protein (Aβ) induces the production of ROS, which upregulates the expression of PGC1α, resulting in increasing mitochondrial biogenesis, fatty acid oxidation and its mRNA expression. However, with the development of AD, a load of Aβ and neurofibrillary tangles ultimately lead to mitochondrial dysfunction, impaired mitochondrial respiration, reduced ATP production, and affect the behavioral brain function in AD. It provides a new idea for improvement or treatment of AD symptoms by activating PGC1α.