Glia in FTLD-GRN: from supporting cast to leading role

Abstract

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.