Vallée Alexandre, Lecarpentier Yves, Guillevin Rémy, Vallée Jean-Noël
Laboratory of Mathematics and Applications (LMA), UMR CNRS 7348, University of Poitiers, CHU de Poitiers, Poitiers, France.
Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien (GHEF), Meaux, France.
Life Sci. 2018 Jan 15;193:141-152. doi: 10.1016/j.lfs.2017.10.033. Epub 2017 Oct 25.
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.
在神经退行性疾病（NDs）中，多种代谢和热力学异常会导致熵率增加。吉布斯自由能、产热、离子电导或细胞内酸度的变化是不可逆过程，这些过程驱动了熵率的改变。本综述聚焦于通过分子信号通路WNT/β-连环蛋白和PPARγ的相反相互作用，在阿尔茨海默病（AD）中细胞能量代谢重编程的热力学影响。在AD中，WNT/β-连环蛋白通路下调而PPARγ上调。经典WNT/β-连环蛋白通路失调会改变代谢酶的热力学行为。WNT/β-连环蛋白通路的下调通过使糖酵解酶（如Glut、PKM2、PDK1、MCT-1、LDH-A）失活但激活PDH，导致氧化应激和细胞死亡。此外，在NDs中，PPARγ失调，而它有助于调节几个关键的昼夜节律基因。AD被认为是一种耗散结构，它与其环境交换能量或物质，远离热力学平衡。远离平衡热力学是由昼夜节律驱动的概念。昼夜节律直接参与调节与细胞能量代谢重编程（促成AD进程）相关的分子通路WNT/β-连环蛋白和PPARγ。
