Targeting TNFα produced by astrocytes expressing amyotrophic lateral sclerosis-linked mutant fused in sarcoma prevents neurodegeneration and motor dysfunction in mice.

Authors

• Brigid K Jensen
• Kevin J McAvoy
• Nicolette M Heinsinger
• Angelo C Lepore
• Hristelina Ilieva
• Aaron R Haeusler
• Davide Trotti
• Piera Pasinelli

Publication/Presentation Date

7-1-2022

Abstract

Genetic mutations that cause amyotrophic lateral sclerosis (ALS), a progressively lethal motor neuron disease, are commonly found in ubiquitously expressed genes. In addition to direct defects within motor neurons, growing evidence suggests that dysfunction of non-neuronal cells is also an important driver of disease. Previously, we demonstrated that mutations in DNA/RNA binding protein fused in sarcoma (FUS) induce neurotoxic phenotypes in astrocytes in vitro, via activation of the NF-κB pathway and release of pro-inflammatory cytokine TNFα. Here, we developed an intraspinal cord injection model to test whether astrocyte-specific expression of ALS-causative FUS

Volume

70

Issue

7

First Page

1426

Last Page

1449

ISSN

1098-1136

Published In/Presented At

Jensen, B. K., McAvoy, K. J., Heinsinger, N. M., Lepore, A. C., Ilieva, H., Haeusler, A. R., Trotti, D., & Pasinelli, P. (2022). Targeting TNFα produced by astrocytes expressing amyotrophic lateral sclerosis-linked mutant fused in sarcoma prevents neurodegeneration and motor dysfunction in mice. Glia, 70(7), 1426–1449. https://doi.org/10.1002/glia.24183

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

35474517

Department(s)

Administration and Leadership

Document Type

Article