Department of Pathology and.
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
J Clin Invest. 2023 Mar 15;133(6):e168215. doi: 10.1172/JCI168215.
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.
神经退行性疾病额颞叶痴呆（FTLD）的一个亚类是由颗粒蛋白前体（GRN）基因突变引起的。在本期 JCI 中，Marsan 及其同事在多个神经胶质细胞谱系——星形胶质细胞、小胶质细胞和少突胶质细胞——中展示了具有疾病特异性的转录谱，这些谱系在 FTLD-GRN 患者和广泛使用的 Grn-/-小鼠模型之间具有高度保守性。此外，作者还表明 Grn-/-星形胶质细胞在小鼠和人类模型中均无法充分维持突触。这项研究有力地证明了神经胶质细胞在神经退行性变中的核心作用，并为深入了解病理生理学、识别潜在的生物标志物和开发治疗方法提供了丰富的资源。
