NeuroMolecular Medicine

, Volume 20, Issue 2, pp 174–204 | Cite as

Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway–PPAR Gamma, Energy Metabolism and Circadian Rhythms

  • Alexandre Vallée
  • Yves Lecarpentier
  • Rémy Guillevin
  • Jean-Noël Vallée
Review Paper


Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington’s disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer’s disease and Parkinson’s disease, WNT/beta-catenin pathway is downregulated while PPAR gamma is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is responsible for the modification of thermodynamics behaviors of metabolic enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis, named Warburg effect, through activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of WNT/beta-catenin pathway leads to oxidative stress and cell death through inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the regulation of several key circadian genes. NDs show many dysregulation in the mediation of circadian clock genes and so of circadian rhythms. Thermodynamics rhythms operate far-from-equilibrium and partly regulate interactions between WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and circadian rhythms are tightly interrelated.


WNT/beta-catenin pathway PPAR gamma Circadian rhythms Neurodegenerative diseases Aerobic glycolysis Oxidative stress 



Acetyl-coenzyme A


Alzheimer’s disease


Amyotrophic lateral sclerosis


Adenomatous polyposis coli


Arrthymogenic right ventricular dysplasia/cardiomyopathy


Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1


Circadian locomotor output cycles kaput








Epithelial-mesenchymal transition






Glucose transporter


Glycogen synthase kinase-3beta


Huntington’s disease


Lactate dehydrogenase

LRP 5/6

Low-density lipoprotein receptor-related protein 5/6


Monocarboxylate lactate transporter-1


Neurodegenerative diseases


Parkinson’s disease


Pyruvate dehydrogenase complex


Pyruvate dehydrogenase kinase





PPAR gamma

Peroxisome proliferator-activated receptor gamma


Peroxisome proliferator-activated receptor gamma coactivator-1 alpha


Phosphatidylinositol 3-kinase-protein kinase B


Retinoid-related orphan receptors


T cell factor/lymphoid enhancer factor




Tricarboxylic acid


Author Contributions

All authors listed, have made contribution to the work, and approved it for submission to publication.

Compliance with Ethical Standards

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.DRCI, Hôpital FochSuresnesFrance
  2. 2.Centre de Recherche CliniqueGrand Hôpital de l’Est FrancilienMeauxFrance
  3. 3.DACTIM, UMR CNRS 7348Université de Poitiers et CHU de PoitiersPoitiersFrance
  4. 4.CHU Amiens PicardieUniversité Picardie Jules Verne (UPJV)AmiensFrance
  5. 5.LMA (Laboratoire de Mathématiques et Applications) CNRS 7348University of PoitiersPoitiersFrance

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