Astrocytic functions and lipid metabolism: Correlations and therapeutic targets in Alzheimer's disease and glioblastoma

Xu Zhang, Rongrong Gao, Liuke Yang, Youwei Zhu, Tiancheng Zhang, Xiaorong Shen, Wenwen Gu, Long Yang, Shenjie Peng
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Abstract

Background

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.

Results

Disturbances in lipid metabolism and astrocytic functions may lead to pathological alterations associated with numerous neurological diseases like Alzheimer's disease (AD) recognised 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 tumour with a poor prognosis.

Conclusions

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.

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星形胶质细胞功能和脂质代谢:阿尔茨海默病和胶质母细胞瘤的相关性和治疗目标
背景 大脑是人体的核心关键器官,其脂质含量仅次于脂肪组织。脂质作为生物膜的主要结构成分,在脑内的大量生物过程中发挥着重要作用,如能量平衡、物质运输、信号转导、神经发生和突触发生,为脑细胞的正常功能提供所需的平衡细胞环境。鉴于脂质在大脑发育和功能中的关键作用,脂质及其代谢在生理上具有重要意义。星形胶质细胞是大脑中数量最多的胶质细胞,参与新陈代谢平衡、血脑屏障维护、神经元支持和串扰等多个过程。 结果 脂质代谢和星形胶质细胞功能的紊乱可能导致与多种神经系统疾病相关的病理改变,如阿尔茨海默病(AD),它被认为是最常见的痴呆病因,会导致严重的进行性记忆和认知障碍,以及预后不良的最具侵袭性的恶性脑肿瘤胶质母细胞瘤(GBM)。 结论 在本文中,我们不仅回顾了脂质代谢改变在 AD 和 GBM 中与星形胶质细胞功能和星形胶质细胞-神经元串联相关的水平和作用,还讨论了参与病理脂质代谢失调可能机制的重要脂质相关代谢物和蛋白质,它们为 AD 和 GBM 的分子靶向疗法提供了潜在的治疗靶点。
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