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.

中文翻译：

---

帕金森病的昼夜节律和能量代谢重编程。

神经退行性疾病 (NDs) 中的几种代谢和热力学异常会增加熵率。吉布斯能量、产热、离子电导或细胞内酸度的变化是促使熵率改变的不可逆过程。本综述侧重于通过分子信号通路 WNT/β-catenin 和 PPARγ 的对比相互作用，在帕金森病 (PD) 中实现细胞能量代谢重编程的热力学意义。在 PD 中，WNT/β-catenin 通路下调，而 PPARγ 上调。代谢酶的热力学行为通过经典 WNT/β-连环蛋白途径的失调而改变。WNT/β-catenin 通路的下调导致低代谢，氧化应激和细胞死亡是通过糖酵解酶（如 Glut、PKM2、PDK1、MCT-1、LDH-A）的失活以及 PDH 的激活来实现的。此外，在 NDs 中，PPARγ 失调，尽管它有助于调节几个关键的昼夜节律基因。PD 过程可以被认为是与远离热力学平衡的环境交换能量或物质的耗散结构。远离平衡的热力学是由昼夜节律驱动的概念，它直接有助于调节参与帕金森病的细胞能量代谢重编程的分子途径 WNT/β-连环蛋白和 PPARγ。PD 过程可以被认为是与远离热力学平衡的环境交换能量或物质的耗散结构。远离平衡的热力学是由昼夜节律驱动的概念，它直接有助于调节参与帕金森病的细胞能量代谢重编程的分子途径 WNT/β-连环蛋白和 PPARγ。PD 过程可以被认为是与远离热力学平衡的环境交换能量或物质的耗散结构。远离平衡的热力学是由昼夜节律驱动的概念，它直接有助于调节参与帕金森病的细胞能量代谢重编程的分子途径 WNT/β-连环蛋白和 PPARγ。