Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target-Reference-Cited by-同舟云学术

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

Published:2023-07-31 Issue:32 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Chiot Aude¹²,Roemer Shanu F.³,Ryner Lisa⁴,Bogachuk Alina¹²,Emberley Katie¹²⁵^ORCID,Brownell Dillon¹²,Jimenez Gisselle A.¹²,Leviten Michael⁴,Woltjer Randall⁶,Dickson Dennis W.³,Steinman Lawrence⁷^ORCID,Ajami Bahareh¹²^ORCID

Affiliation:

1. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239

2. Department of Behavioral and Systems Neuroscience, Oregon Health and Science University, Portland, OR 97239

3. Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224

4. Pasithea Therapeutics, Molecular Research Laboratories, South San Francisco, CA 94080

5. Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health and Science University, Portland, OR 97239

6. Department of Pathology, Oregon Health and Science University, Portland, OR 97239

7. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305

Abstract

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 (SOD1 G93A ). 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 SOD1 G93A 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.

Funder

Fight Motor Neuron Disease Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2306731120

Reference39 articles.

1. Drug discovery and amyotrophic lateral sclerosis: Emerging challenges and therapeutic opportunities

2. Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice

3. D. R. Beers Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U.S.A. 103 16021–16026 (2006).

4. Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia

5. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice

Cited by 1 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and generate neuroprotection in the SOD1^G93Amouse model of ALS via activation of the IGF–Akt–mTOR axis pathway;2023-11-16