Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target.

Aude Chiot, Shanu F Roemer, Lisa Ryner, Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A Jimenez, Michael Leviten, Randall Woltjer, Dennis W Dickson, Lawrence Steinman, Bahareh Ajami

Proceedings of the National Academy of Sciences of the United States of America 2023 Jul 31

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Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single-cell mass cytometry (CyTOF) analysis revealed prominent expression of α5 integrin in microglia and macrophages in a superoxide dismutase-1 G93A mouse model of ALS (SOD1G93A). In postmortem tissues from ALS patients with various clinical ALS phenotypes and disease duration, α5 integrin is prominent in motor pathways of the central and peripheral nervous system and in perivascular zones associated with the blood-brain barrier. In SOD1G93A mice, administration of a monoclonal antibody against α5 integrin increased survival compared to an isotype control and improved motor function on behavioral testing. Together, these findings in mice and in humans suggest that α5 integrin is a potential therapeutic target in ALS.

Citation

Aude Chiot, Shanu F Roemer, Lisa Ryner, Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A Jimenez, Michael Leviten, Randall Woltjer, Dennis W Dickson, Lawrence Steinman, Bahareh Ajami. Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target. Proceedings of the National Academy of Sciences of the United States of America. 2023 Jul 31;120(32):e2306731120