Circadian Rhythms and Energy Metabolism Reprogramming in Parkinson's Disease.

Entropy rate is increased by several metabolic and thermodynamic abnormalities in neurodegenerative diseases (NDs). Changes in Gibbs energy, heat production, ionic conductance or intracellular acidity are irreversible processes impelling modifications of the entropy rate. The present review focuses on the thermodynamic implications in the reprogramming of cellular energy metabolism enabling in Parkinson's disease (PD) through the contrasting interplay of the molecular signaling pathways WNT/ β-catenin and PPARγ. In PD, WNT/β-catenin pathway is downregulated while PPARγ is upregulated. Thermodynamic behaviors of metabolic enzymes are modified by dysregulation of the canonical WNT/β-catenin pathway. Downregulation of WNT/β-catenin pathway leads to hypometabolism, oxidative stress and cell death through inactivation of glycolytic enzymes such as Glut, PKM2, PDK1, MCT-1, LDH-A but also to activation of PDH. In addition, in NDs, PPARγ is dysregulated even though it contributes to the regulation of several key circadian genes. PD processes may be considered as dissipative structures that exchange energy or matter with their environment far-from the thermodynamic equilibrium. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms, which directly contribute to regulation of the molecular pathways WNT/β-catenin and PPARγ involved in the reprogramming of cellular energy metabolism enabling in Parkinson's disease.