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通过新型生物技术策略靶向反应性星形胶质细胞。

Targeting reactive astrogliosis by novel biotechnological strategies.

机构信息

Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.

出版信息

Biotechnol Adv. 2012 Jan-Feb;30(1):261-71. doi: 10.1016/j.biotechadv.2011.06.016. Epub 2011 Jul 5.

Abstract

Neuroglial cells are fundamental for control of brain homeostasis and synaptic plasticity. Decades of pathological and physiological studies have focused on neurons in neurodegenerative disorders, but it is becoming increasingly evident that glial cells play an irreplaceable part in brain homeostasis and synaptic plasticity. Animal models of brain injury and neurodegenerative diseases have largely contributed to current understanding of astrocyte-specific mechanisms participating in brain function and neurodegeneration. Specifically, gliotransmission (presence of glial neurotransmitters, and their receptors and active transporters), trophic support (release, maturation and degradation of neurotrophins) and metabolism (production of lactate and GSH components) are relevant aspects of astrocyte function in neuronal metabolism, synaptic plasticity and neuroprotection. Morpho-functional changes of astrocytes and microglial cells after traumatic or toxic insults to the central nervous system (namely, reactive gliosis) disrupt the complex neuro-glial networks underlying homeostasis and connectivity within brain circuits. Thus, neurodegenerative diseases might be primarily regarded as gliodegenerative processes, in which profound alterations of glial activation have a clear impact on progression and outcomes of neuropathological processes. This review provides an overview of current knowledge of astrocyte functions in the brain and how targeting glial-specific pathways might ultimately impact the development of therapies for clinical management of neurodegenerative disorders.

摘要

神经胶质细胞对于控制大脑内环境稳定和突触可塑性至关重要。几十年来,病理性和生理学研究都集中在神经退行性疾病的神经元上,但越来越明显的是,胶质细胞在大脑内环境稳定和突触可塑性中起着不可或缺的作用。脑损伤和神经退行性疾病的动物模型在很大程度上促进了我们对星形胶质细胞特异性机制参与大脑功能和神经退行性变的理解。具体来说,神经胶质传递(神经胶质递质及其受体和主动转运体的存在)、营养支持(神经营养因子的释放、成熟和降解)和代谢(乳酸和 GSH 成分的产生)是星形胶质细胞在神经元代谢、突触可塑性和神经保护中功能的相关方面。中枢神经系统受到创伤或毒性损伤后星形胶质细胞和小胶质细胞的形态和功能变化(即反应性神经胶质增生)破坏了内环境稳定和脑回路连接性所依赖的复杂神经胶质网络。因此,神经退行性疾病可能主要被视为神经胶质变性过程,其中胶质细胞激活的深刻改变对神经病理过程的进展和结果有明显影响。本综述概述了星形胶质细胞在大脑中的功能的现有知识,以及靶向胶质细胞特异性途径最终如何可能影响神经退行性疾病临床治疗的发展。

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