Reprogramming energetic metabolism in Alzheimer's disease
Entropy rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Changes in Gibbs energy, heat production, ionic conductance or intracellular acidity are irreversibles processes which driven modifications of the entropy rate. The present review focusses on the thermodynamic implications in the reprogramming of cellular energy metabolism enabling in Alzheimer's disease (AD) through the opposite interplay of the molecular signaling pathways WNT/β-catenin and PPARγ.
In AD, WNT/β-catenin pathway is downregulated while PPARγ is upregulated. Thermodynamics behaviors of metabolic enzymes are modified by dysregulation of the canonical WNT/β-catenin pathway. Downregulation of WNT/β-catenin pathway leads to oxidative stress and cell death through inactivation of glycolytic enzymes such as Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPARγ is dysregulated whereas it contributes to the regulation of several key circadian genes.
AD is considered as a dissipative structure that exchanges energy or matter with its environment far from the thermodynamic equilibrium. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms. Circadian rhythms directly participate in regulating the molecular pathways WNT/β-catenin and PPARγ involved in the reprogramming of cellular energy metabolism enabling AD processes.