Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential

Justin You; Mohieldin M M Youssef; Jhune Rizsan Santos; Jooyun Lee; Jeehye Park

doi:10.3390/biology12101307

Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential

Biology (Basel). 2023 Oct 3;12(10):1307. doi: 10.3390/biology12101307.

Authors

Justin You¹, Mohieldin M M Youssef¹, Jhune Rizsan Santos^{1

2}, Jooyun Lee^{1

2}, Jeehye Park^{1

2}

Affiliations

¹ Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
² Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.

Abstract

Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia and astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by a specific molecular profile or function depending on the different contexts of development, health, aging, and disease. Accumulating evidence from ALS rodent and cell models has demonstrated neuroprotective and neurotoxic functions from microglia and astrocytes. In this review, we focused on the recent advancements of knowledge in microglial and astrocytic states and nomenclature, the landmark discoveries demonstrating a clear contribution of microglia and astrocytes to ALS pathogenesis, and novel therapeutic candidates leveraging these cells that are currently undergoing clinical trials.

Keywords: C9ORF72; SOD1; TDP-43; amyotrophic lateral sclerosis (ALS); astrocyte; clinical trials; microglia; neurodegeneration.

Publication types

Review

Grants and funding

This work was funded by the ALS Society of Canada, Brain Canada, ALS Association, and Canadian Institutes of Health Research (CIHR). J.R.S. is supported by a Catalyzing the Talent Pipeline Scholarship from the David Dime Family Catalyst Initiative in Molecular Genetics at the University of Toronto. J.L. is supported by the Canada Graduate Scholarship-Master’s Program, University of Toronto-Fellowship, and Restracomp from The Hospital of Sick Children.