Astrocyte, Lipid Metabolism in Alzheimer’s Disease and Glioblastoma

Abstract

The brain is a central key organ of the body containing the second highest lipid content only after adipose tissue. Lipids as the main structural components of biological membranes play important roles in a vast number of biological processes within the brain such as energy homeostasis, material transport, signal transduction, neurogenesis and synaptogenesis, providing a balanced cellular environment required for proper functioning of brain cells. Lipids and their metabolism are of great physiological importance in view of the crucial roles of lipids in brain development and function. Astrocytes are the most abundant glial cells in the brain and involved in various processes including metabolic homeostasis, blood brain barrier maintenance, neuronal support and crosstalk. Disturbances in lipid metabolism and astrocytic functions may lead to pathological alterations associated with numerous neurological diseases like Alzheimer's Disease (AD) recognized as the most frequent cause of dementia leading to major progressive memory and cognitive deficits as well as Glioblastoma (GBM) known as the most aggressive malignant brain tumor with a poor prognosis. Herein, we not only review the level and role of altered lipid metabolism in correlation with astrocytic function and astrocyte-neuron crosstalk in AD and GBM, but also discuss important lipid-related metabolites and proteins participating in possible mechanisms of pathologically dysregulated lipid metabolism, offering potential therapeutic targets in targeted molecular therapies for AD and GBM.

Neuropathology-based GWAS for Alzheimer’s disease reveals novel susceptibility loci and highlights sex-specific pathways

“…Concerning the potential utilization of ACSBG1 blood levels as a biomarker, ACSBG1 is prominently concentrated in the brain, primarily within astrocytes 50 . In vitro studies have demonstrated that ACSBG1 knockdown leads to reduced lipid oxidation, closely associated with AD 51,52 It is important to note that further research with larger sample sizes is required to confirm and expand upon our findings.…”