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星形胶质细胞是中枢神经系统中数量最多的细胞,从引导轴突、突触支持到控制血-脑脊液屏障及脑血流,发挥多种作用。发挥这些作用需要通过大量不同类型的星形胶质细胞进行。本文对星形胶质细胞的功能,尤其是保持突触平衡、调节神经元信号传导、保护氧化损伤下的神经元和决定内源性神经前体细胞分化方面的作用进行综述。本文还重点讨论近年星形胶质细胞在运动神经元病(MND)中的作用方面的研究,强调其在细胞替代治疗中作为治疗靶标和治疗剂的潜能。在20%家族性MND中涉及到的铜锌超氧化物歧化酶(SOD1)基因,其必须表达在胶质细胞和运动神经元中来诱导小鼠疾病模型的疾病状态。在星形胶质细胞中选择性减少突变SOD1(mSOD1)不会影响疾病发作,可延缓疾病进展;但减少运动神经元中的mSOD1可推迟疾病发作,延缓早期病程,对寿命无影响。这提示胶质细胞在MND中可作为潜在的治疗靶标。然而,对星形胶质细胞特异性标志物、前体细胞、亚型的认识缺乏意味着对其发育/分化、应对损伤的了解落后于对其功能的认识。只有深入理解这些问题才能有效运用星形胶质细胞靶向或替代治疗慢性中枢神经系统疾病,如MND。
Astrocytes are the most abundant cells in the central nervous system and play a variety of roles, from guiding axons and synaptic support to controlling the blood-brain barrier and cerebral blood flow. These roles need to be performed by a large number of different types of astrocytes. This review summarizes the functions of astrocytes, in particular the maintenance of synaptic balance, the regulation of neuronal signaling, the protection of neurons under oxidative damage, and the decision to differentiate endogenous neural progenitor cells. This article also focuses on the role of astrocytes in motor neuron disease (MND) in recent years and highlights their potential as therapeutic targets and therapeutic agents in cell replacement therapy. The copper-zinc superoxide dismutase (SOD1) gene involved in 20% of familial MNDs must be expressed in glial cells and motor neurons to induce disease states in mouse disease models. Selectively reducing mutant SOD1 (mSOD1) in astrocytes does not affect the onset of the disease and slows the progression of the disease; however, reducing mSOD1 in motor neurons can delay onset of disease, delay early course, and have no effect on longevity. This suggests that glial cells may serve as potential therapeutic targets in MND. However, a lack of understanding of astrocyte-specific markers, precursor cells, and subtypes means that their understanding of the development / differentiation and damage response lags behind their understanding of their function. Only in-depth understanding of these issues in order to effectively use astrocyte targeting or alternative treatment of chronic central nervous system diseases such as MND.