Elevated a5 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

doi:10.1073/pnas.2306731120

Elevated a5 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

Research output: Contribution to journal › Article › peer-review

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 a5 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, a5 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 a5 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 a5 integrin is a potential therapeutic target in ALS.

Original language	English (US)
Article number	e2306731120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Issue number	32
DOIs	https://doi.org/10.1073/pnas.2306731120
State	Published - Aug 8 2023

Keywords

a5 integrin
amyotrophic lateral sclerosis
macrophages
microglial cells
therapeutic

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2306731120

Cite this

Chiot, A., Roemer, S. F., Ryner, L., Bogachuk, A., Emberley, K., Brownell, D., Jimenez, G. A., Leviten, M., Woltjer, R., Dickson, D. W., Steinman, L., & Ajami, B. (2023). Elevated a5 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, 120(32), Article e2306731120. https://doi.org/10.1073/pnas.2306731120

Chiot, A, Roemer, SF, Ryner, L, Bogachuk, A, Emberley, K, Brownell, D, Jimenez, GA, Leviten, M, Woltjer, R, Dickson, DW, Steinman, L & Ajami, B 2023, 'Elevated a5 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, vol. 120, no. 32, e2306731120. https://doi.org/10.1073/pnas.2306731120

@article{f3f09f621b2d4b859a2303be1ab558f5,

title = "Elevated a5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target",

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 a5 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, a5 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 a5 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 a5 integrin is a potential therapeutic target in ALS.",

keywords = "a5 integrin, amyotrophic lateral sclerosis, macrophages, microglial cells, therapeutic",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s).",

year = "2023",

month = aug,

day = "8",

doi = "10.1073/pnas.2306731120",

language = "English (US)",

volume = "120",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "32",

}

TY - JOUR

T1 - Elevated a5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target

AU - Chiot, Aude

AU - Roemer, Shanu F.

AU - Ryner, Lisa

AU - Bogachuk, Alina

AU - Emberley, Katie

AU - Brownell, Dillon

AU - Jimenez, Gisselle A.

AU - Leviten, Michael

AU - Woltjer, Randall

AU - Dickson, Dennis W.

AU - Steinman, Lawrence

AU - Ajami, Bahareh

PY - 2023/8/8

Y1 - 2023/8/8

N2 - 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 a5 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, a5 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 a5 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 a5 integrin is a potential therapeutic target in ALS.

AB - 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 a5 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, a5 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 a5 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 a5 integrin is a potential therapeutic target in ALS.

KW - a5 integrin

KW - amyotrophic lateral sclerosis

KW - macrophages

KW - microglial cells

KW - therapeutic

UR - http://www.scopus.com/inward/record.url?scp=85166387376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85166387376&partnerID=8YFLogxK

U2 - 10.1073/pnas.2306731120

DO - 10.1073/pnas.2306731120

M3 - Article

C2 - 37523555

AN - SCOPUS:85166387376

SN - 0027-8424

VL - 120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 32

M1 - e2306731120

ER -

Elevated a5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this