Abstract
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.
Highlights
Parkinson's disease (PD) is a major neurodegenerative disease with a progressive degeneration of neurons containing dopamine in the substantia nigra pars compacta
We focused this review on the opposed interactions observed in PD between the canonical WNT/β-catenin pathway and peroxisome proliferator-activated γ (PPARγ) and their circadian rhythms and energy metabolism implications
From a thermodynamic point of view, neurodegenerative diseases (NDs) processes are like many irreversible processes which can occur by changing the entropy production rate
Summary
Parkinson's disease (PD) is a major neurodegenerative disease with a progressive degeneration of neurons containing dopamine in the substantia nigra pars compacta. We focused this review on the opposed interactions observed in PD between the canonical WNT/β-catenin pathway and PPARγ and their circadian rhythms and energy metabolism implications. This association with β-catenin transiently converts TCF/LEF complex from a transcriptional repressor into an activator of specific target genes involved throughout development, cell survival and proliferation.
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