Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases

Abstract

Astrocytes play a pivotal role in maintaining brain energy homeostasis, supporting neuronal function through glycolysis and lipid metabolism. This review explores the metabolic intricacies of astrocytes in both physiological and pathological conditions, highlighting their adaptive plasticity and diverse functions. Under normal conditions, astrocytes modulate synaptic activity, recycle neurotransmitters, and maintain the blood–brain barrier, ensuring a balanced energy supply and protection against oxidative stress. However, in response to central nervous system pathologies such as neurotrauma, stroke, infections, and neurodegenerative diseases like Alzheimer’s and Huntington’s disease, astrocytes undergo significant morphological, molecular, and metabolic changes. Reactive astrocytes upregulate glycolysis and fatty acid oxidation to meet increased energy demands, which can be protective in acute settings but may exacerbate chronic inflammation and disease progression. This review emphasizes the need for advanced molecular, genetic, and physiological tools to further understand astrocyte heterogeneity and their metabolic reprogramming in disease states.