Reprogramming energetic metabolism in Alzheimer's disease

Area of Science:

• Thermodynamics
• Cellular Metabolism
• Neurodegenerative Diseases

Background:

• Neurodegenerative diseases (NDs) exhibit altered entropy rates due to metabolic and thermodynamic abnormalities.
• Changes in Gibbs energy, heat production, and cellular acidity are irreversible processes influencing entropy rate.
• Alzheimer's disease (AD) involves reprogramming of cellular energy metabolism.

Purpose of the Study:

• To review the thermodynamic implications in Alzheimer's disease (AD) energy metabolism.
• To examine the interplay between WNT/β-catenin and PPARγ pathways in AD.
• To understand the role of circadian rhythms in AD pathogenesis.

Main Methods:

• Review of literature on thermodynamics in neurodegenerative diseases.
• Analysis of molecular signaling pathways (WNT/β-catenin, PPARγ) in AD.
• Exploration of circadian rhythm influences on cellular metabolism.

Main Results:

• In AD, WNT/β-catenin is downregulated, and PPARγ is upregulated, altering metabolic enzyme function.
• WNT/β-catenin downregulation leads to oxidative stress and cell death via glycolytic enzyme inactivation.
• PPARγ dysregulation impacts circadian gene regulation, contributing to AD.
• AD is characterized as a dissipative structure influenced by far-from-equilibrium thermodynamics and circadian rhythms.

Conclusions:

• Thermodynamic abnormalities and circadian rhythms are critical in AD's metabolic reprogramming.
• Dysregulation of WNT/β-catenin and PPARγ pathways significantly contributes to AD pathogenesis.
• Understanding these thermodynamic and circadian influences offers insights into AD mechanisms.