Targeting Astrocytic Connexin 43 Mitigates Glutamate-Driven Motor Neuron Stress in Late-Onset Spinal Muscular Atrophy.

ABSTRACT: 5q-associated Spinal Muscular Atrophy (SMA) is a hereditary neuromuscular disorder caused by mutations in the survival of motor neuron 1 (SMN1) gene, leading to progressive muscle weakness, and atrophy. While traditionally viewed as a motor neuron (MN)-specific disease, emerging evidence highlights the critical role of astrocytes, particularly in regulating extracellular glutamate and mitigating MN toxicity. Here, we investigated astrocytic gap junctions with a focus on connexin 43 (Cx43). Using in vivo and in vitro approaches-including a late-onset SMA mouse model, human-derived astrocytes, and murine astrocyte cultures-we analyzed Cx43 expression and localization via genetic modification, immunostaining, Western blotting, and quantitative PCR. Functional consequences were a

SUBMITTER: Salmanian S 

PROVIDER: S-EPMC12691144 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature