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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

Abstract

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.

Keywords

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

Abbreviations

Acetyl-coA

Acetyl-coenzyme A

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

APC

Adenomatous polyposis coli

ARVC

Arrthymogenic right ventricular dysplasia/cardiomyopathy

Bmal1

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

Clock

Circadian locomotor output cycles kaput

COX-2

Cyclooxygenase-2

Cry

Cryptochrome

Dsh

Disheveled

EMT

Epithelial-mesenchymal transition

Fzd

Frizzled

GK

Glucokinase

GLUT

Glucose transporter

GSK-3beta

Glycogen synthase kinase-3beta

HD

Huntington’s disease

LDH

Lactate dehydrogenase

LRP 5/6

Low-density lipoprotein receptor-related protein 5/6

MCT-1

Monocarboxylate lactate transporter-1

NDs

Neurodegenerative diseases

PD

Parkinson’s disease

PDH

Pyruvate dehydrogenase complex

PDK

Pyruvate dehydrogenase kinase

Per

Period

PFK-1

Phosphofructokinase-1

PPAR gamma

Peroxisome proliferator-activated receptor gamma

PGC-1alpha

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha

PI3K-Akt

Phosphatidylinositol 3-kinase-protein kinase B

RORs

Retinoid-related orphan receptors

TCF/LEF

T cell factor/lymphoid enhancer factor

TZD

Thiazolidinedione

TCA

Tricarboxylic acid

Notes

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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Copyright information

© 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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