Astrocyte Lipid Droplet Dynamics Orchestrate Neurological Disorders and Therapeutic Horizons.

Abstract

Astrocytes, the predominant glial cells in the central nervous system (CNS), play a pivotal role in maintaining neuronal homeostasis and function. Accumulating evidence suggests that astrocytic dysfunction is closely associated with the pathogenesis of various neurological disorders, including neurodegenerative diseases, ischemic stroke (IS), epilepsy, and glioma. Lipid droplets (LDs), ubiquitous intracellular lipid storage organelles, exhibit metabolic abnormalities that are commonly observed in these neurological conditions, particularly in astrocytes, where LD metabolic dysregulation may serve as a critical link between glial dysfunction and neuronal damage. However, a systematic understanding of the regulatory mechanisms governing LD metabolism in astrocytes and their relationship to the pathogenesis of neurological diseases remains elusive. This article reviews the biology and pathology of astrocytes and summarizes the characteristics, regulatory factors, and abnormalities of LD metabolism in astrocytes, highlighting its association with neurodegenerative diseases, stroke, epilepsy, and glioma. Finally, we propose future research directions, emphasizing the need for integrative multiomics approaches and innovative regulatory technologies to elucidate the role of astrocytic LD metabolism in neurological disorders. Understanding the dysregulation of LD metabolism in astrocytes may provide novel insights into disease etiology and facilitate the development of glial-targeted diagnostic and therapeutic strategies.