The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis.

ABSTRACT: Systemic immune changes have been implicated in amyotrophic lateral sclerosis (ALS), but precise mechanisms and cellular targets remain unknown. Neuromuscular junction (NMJ) denervation is another major pathophysiological event in ALS, but it remains unclear whether immune system dysregulation contributes to this process. Here, we report leukocyte and macrophage infiltration in ALS patient-derived skeletal muscle biopsies. Immune cell infiltration was replicated across the hTDP-43, TDP-43^A315T (male only) and TDP-43^M337V mouse models, occurring from pre-symptomatic stages and targeted to NMJ-enriched muscle regions. Proteomic analysis implicated the CCL2-CCR2 axis as a driving factor. CCL2⁺ cells were enriched around NMJs in hTDP-43 mice, and in ALS patient

SUBMITTER: Nogradi B 

PROVIDER: S-EPMC12316999 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature