Astrocyte adaptation in Alzheimer's disease: a focus on astrocytic P2X7R.
Astrocyte adaptation in Alzheimer's disease: a focus on astrocytic P2X7R.
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DOI：
10.1042/ebc20220079
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发表时间：
2023-03-03
影响因子：
6.4
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中科院分区：
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星形胶质细胞是中枢神经系统（CNS）的关键稳态和防御细胞。它们在发育期间和成年期承担许多功能，通过与神经组织的其他细胞成分进行精细调节的通信来支持和保护大脑。在阿尔茨海默病（AD）中，星形胶质细胞经历异质性形态、分子和功能改变，表现为反应性重塑、虚弱和功能丧失。在晚期AD中，反应性星形胶质细胞与淀粉样β（Aβ）斑块和神经元缠结密切相关。星形胶质细胞对AD的特定贡献可能沿着疾病过程发展，包括其信号传导、与病理性蛋白质聚集体的相互作用、代谢和突触损伤的改变。在这篇综述中，我们专注于嘌呤能受体，P2X7R，并讨论的证据表明，P2X7R激活有助于改变AD星形胶质细胞的功能。相对于非痴呆对照，P2X7R的表达在AD脑中增加，并且动物研究已经表明，P2X7R拮抗作用改善淀粉样变性和tau蛋白病模型中的认知和突触损伤。虽然P2X7R激活可以诱导炎症信号通路，特别是在小胶质细胞中，我们在这里特别关注星形胶质细胞P2X7R对AD中突触变化和蛋白质聚集体清除的贡献，突出了这种嘌呤受体激活的细胞特异性作用，可以靶向减缓疾病进展。
Astrocytes are key homeostatic and defensive cells of the central nervous system (CNS). They undertake numerous functions during development and in adulthood to support and protect the brain through finely regulated communication with other cellular elements of the nervous tissue. In Alzheimer’s disease (AD), astrocytes undergo heterogeneous morphological, molecular and functional alterations represented by reactive remodelling, asthenia and loss of function. Reactive astrocytes closely associate with amyloid β (Aβ) plaques and neurofibrillary tangles in advanced AD. The specific contribution of astrocytes to AD could potentially evolve along the disease process and includes alterations in their signalling, interactions with pathological protein aggregates, metabolic and synaptic impairments. In this review, we focus on the purinergic receptor, P2X7R, and discuss the evidence that P2X7R activation contributes to altered astrocyte functions in AD. Expression of P2X7R is increased in AD brain relative to non-demented controls, and animal studies have shown that P2X7R antagonism improves cognitive and synaptic impairments in models of amyloidosis and tauopathy. While P2X7R activation can induce inflammatory signalling pathways, particularly in microglia, we focus here specifically on the contributions of astrocytic P2X7R to synaptic changes and protein aggregate clearance in AD, highlighting cell-specific roles of this purinoceptor activation that could be targeted to slow disease progression.