Glia in FTLD-GRN: from supporting cast to leading role.
Glia in FTLD-GRN: from supporting cast to leading role.
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DOI：
10.1172/jci168215
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发表时间：
2023-03-15
影响因子：
15.9
通讯作者：
Barmada, Sami J.
中科院分区：
文献类型：
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作者：
Pinarbasi, Emile S.;Barmada, Sami J.
神经退行性疾病额颞叶变性（FTLD）的一个子集是由颗粒蛋白前体（GRN）基因突变引起的。在这一期的JCI中，Marsan及其同事证明了多种神经胶质细胞谱系-星形胶质细胞，小胶质细胞和少突胶质细胞-中的疾病特异性转录谱在FTLD-GRN患者和广泛使用的Grn-/-小鼠模型之间高度保守。此外，作者表明Grn-/-星形胶质细胞在小鼠和人类模型中都不能充分维持突触。这项研究为神经胶质细胞在神经退行性变中的核心作用提供了一个令人信服的论据，并为扩大对病理生理学的机械洞察力，识别潜在的生物标志物和开发治疗方法创造了丰富的资源。
A subset of the neurodegenerative disease frontotemporal lobar degeneration (FTLD) is caused by mutations in the progranulin (GRN) gene. In this issue of the JCI, Marsan and colleagues demonstrate disease-specific transcriptional profiles in multiple glial cell lineages — astrocytes, microglia, and oligodendroglia — that are highly conserved between patients with FTLD-GRN and the widely used Grn–/– mouse model. Additionally, the authors show that Grn–/– astrocytes fail to adequately maintain synapses in both mouse and human models. This study presents a compelling argument for a central role for glia in neurodegeneration and creates a rich resource for extending mechanistic insight into pathophysiology, identifying potential biomarkers, and developing therapeutic approaches.