Conditional depletion of Fus in oligodendrocytes leads to motor hyperactivity and increased myelin deposition associated with Akt and cholesterol activation.

ABSTRACT: Fused in sarcoma (FUS) is a predominantly nuclear multifunctional RNA/DNA-binding protein that regulates multiple aspects of gene expression. FUS mutations are associated with familial amyotrophic lateral sclerosis (fALS) and frontotemporal lobe degeneration (FTLD) in humans. At the molecular level, the mutated FUS protein is reduced in the nucleus but accumulates in cytoplasmic granules. Oligodendrocytes (OL) carrying clinically relevant FUS mutations contribute to non-cell autonomous motor neuron disease progression, consistent with an extrinsic mechanism of disease mediated by OL. Knocking out FUS globally or in neurons lead to behavioral abnormalities that are similar to those present in FTLD. In this study, we sought to investigate whether an extrinsic mechanism mediated by loss of FU

SUBMITTER: Guzman KM 

PROVIDER: S-EPMC7772959 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature