HUN-REN Biological Research Centre, Szeged 
Aug 6, 2025 | News
Amyotrophic lateral sclerosis (ALS) is a progressive, incurable neurodegenerative disorder, characterized by systemic immune alterations and denervation of the neuromuscular junctions (NMJs). The exact mechanisms that lead to NMJ degeneration are unknown.
Cytokines are signalling molecules that play a crucial role in cell-to-cell communication. Chemokines are a subgroup of the cytokine family, capable of inducing local chemotaxis. Among these proteins, the chemokine CCL2 is considered to be a major pro-inflammatory marker, able to initiate robust immune cell infiltration (through its binding to CCR2 receptor), contributing to the pathomechanism of inflammatory disorders.
Researchers at the Institute of Biophysics and the Core Facilities of the HUN-REN BRC and the Department of Neurology at the University of Szeged, along with international collaborators found leukocyte and macrophage infiltration in the muscle biopsy samples of ALS patients. These alterations were also detected in multiple transgenic mice models of ALS, already present at presymptomatic disease stages. Proteomic analysis revealed that the CCL2-CCR2 axis plays a major role in this immune cell activation, and CCL2-positive cells primarily localized around NMJs. Furthermore, they demonstrated that the local injection of CCL2-neutralizing antibodies decreased leukocyte infiltration and ameliorated NMJ denervation, revealing a potential therapeutic target to slow down disease progression.
The results were published in Nature Communications (https://doi.org/10.1038/s41467-025-62351-3).