Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid Pathology?
Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid Pathology?
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发表时间：
2013-08
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通讯作者：
Liang-Jun Yan;Ming Xiao;Ran Chen;Z. Cai
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作者：
Liang-Jun Yan;Ming Xiao;Ran Chen;Z. Cai
星形胶质细胞是大脑中最重要的能量调节器，支持大脑的能量需求。同时，大量研究表明，AD患者脑葡萄糖代谢受损与星形胶质细胞代谢异常密切相关。事实上，淀粉样蛋白斑块和扰动的星形胶质细胞内稳态之间的相互作用有助于AD发病机制，并且星形胶质细胞代谢功能障碍被认为是通过氧化应激和神经炎症导致Aβ病理学的触发因素。此外，星形胶质细胞代谢功能障碍可以通过调节β-分泌酶、γ-分泌酶和α-分泌酶对淀粉样蛋白前体蛋白（APP）的蛋白水解加工来调节Aβ的产生，并且还可以调节APP翻译后修饰，例如糖基化、磷酸化和酪氨酸硫酸化。虽然已知星形胶质细胞的代谢功能障碍导致Aβ清除失败，但也有报道称，这种功能障碍具有神经保护特性，并且没有表现出有害结果。因此，星形胶质细胞代谢功能障碍在Aβ病理中的确切作用仍有待进一步研究。
Astrocytes, the most important energy regulator in the brain, support brain energy needs. In the meantime, numerous studies have demonstrated that impaired brain glucose metabolism is closely linked to abnormal astrocytic metabolism in AD. Indeed, the interaction between amyloid plaques and perturbed astrocytic homeostasis contributes to AD pathogenesis and astrocytic metabolic dysfunction is thought to be a trigger for Aβ pathology through oxidative stress and neuroinflammation Moreover, astrocytic metabolic dysfunction may regulate Aβ generation via modulating proteolytic processing of amyloid precursor protein (APP) by β-secretase, γ-secretase, and α-secretase, and may also modulate APP post-translational modifications such as glycosylation, phosphorylation, and tyrosine sulfation. While it is known that metabolic dysfunction of astrocytes contributes to the failure of Aβ clearance, it has also been reported that such dysfunction has neuroprotective property and exhibits no detrimental outcomes. Therefore, the exact role of astrocytic metabolic dysfunction in Aβ pathology remains to be further investigated.