Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

Abstract

Neurodegenerative diseases (ND) are conditions defined by progressive deterioration of the structure and function of the nervous system. Some major examples include Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). These diseases lead to various dysfunctions, like impaired cognition, memory, and movement. Chronic neuroinflammation may underlie numerous neurodegenerative disorders. Microglia, an important immunocell in the brain, plays a vital role in defending against neuroinflammation. When exposed to different stimuli, microglia are activated and assume different phenotypes, participating in immune regulation of the nervous system and maintaining tissue homeostasis. The immunological activity of activated microglia is affected by glucose metabolic alterations. However, in the context of chronic neuroinflammation, specific alterations of microglial glucose metabolism and their mechanisms of action remain unclear. Thus, in this paper, we review the glycometabolic reprogramming of microglia in ND. The key molecular targets and main metabolic pathways are the focus of this research. Additionally, this study explores the mechanisms underlying microglial glucose metabolism reprogramming in ND and offers an analysis of the most recent therapeutic advancements. The ultimate aim is to provide insights into the development of potential treatments for ND.