Loss of Tmem106b exacerbates FTLD pathologies and causes motor deficits in progranulin-deficient mice.

ABSTRACT: Progranulin (PGRN) and transmembrane protein 106B (TMEM106B) are important lysosomal proteins implicated in frontotemporal lobar degeneration (FTLD) and other neurodegenerative disorders. Loss-of-function mutations in progranulin (GRN) are a common cause of FTLD, while TMEM106B variants have been shown to act as disease modifiers in FTLD. Overexpression of TMEM106B leads to lysosomal dysfunction, while loss of Tmem106b ameliorates lysosomal and FTLD-related pathologies in young Grn^-/- mice, suggesting that lowering TMEM106B might be an attractive strategy for therapeutic treatment of FTLD-GRN. Here, we generate and characterize older Tmem106b^-/- Grn^-/- double knockout mice, which unexpectedly show severe motor deficits and spinal cord motor neuron and myeli

SUBMITTER: Zhou X 

PROVIDER: S-EPMC7534638 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature