Cited by 175Amyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research Studies

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Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia

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Lall, Deepti, Baloh, Robert H.·2017·Journal of Clinical Investigation

DOI 10.1172/jci90607PMC PMC5669558

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Abstract

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that is characterized by loss of motor neurons and shows clinical, pathological, and genetic overlap with frontotemporal dementia (FTD). Activated microglia are a universal feature of ALS/FTD pathology; however, their role in disease pathogenesis remains incompletely understood. The recent discovery that ORF 72 on chromosome 9 (C9orf72), the gene most commonly mutated in ALS/FTD, has an important role in myeloid cells opened the possibility that altered microglial function plays an active role in disease. This Review highlights the contribution of microglia to ALS/FTD pathogenesis, discusses the connection between autoimmunity and ALS/FTD, and explores the possibility that C9orf72 and other ALS/FTD genes may have a "dual effect" on both neuronal and myeloid cell function that could explain a shared propensity for altered systemic immunity and neurodegeneration.

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Authors: Lall, D., & Baloh, R. H.
Affiliations: Regenerative Medicine Institute (MX)
Cedars-Sinai Medical Center (US)
Corresponding author: Baloh, Robert H.
ORCID: Baloh, Robert H.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2017-07-24
Volume: 127
Issue: 9
Pages: 3250-3258
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci90607
PMC: PMC5669558
OpenAlex: W2736657964
Cited by: 175
References: 150
Citations by year: 2026: 14 · 2025: 16 · 2024: 11 · 2023: 22 · 2022: 27 · 2021: 16 · 2020: 20 · 2019: 28 · 2018: 16 · 2017: 5
FWCI: 2.50
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Target ALS
Cedars-Sinai Medical Center
National Institutes of Health
National Institute of Neurological Disorders and Stroke (R01NS097545, R01NS069669)
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Keywords: microglia, C9orf72, amyotrophic lateral sclerosis, frontotemporal dementia, neuroinflammation, autoimmunity, myeloid cells, neurodegeneration, pathogenesis, systemic immunity
MeSH terms: Superoxide Dismutase-1, C9orf72 Protein, Amyotrophic Lateral Sclerosis, Animals, DNA-Binding Proteins, Humans, Inflammation, Motor Neurons, Mutation, Phenotype, Proteins, Autoimmunity, Microglia, Disease Progression, Genetic Predisposition to Disease, Myeloid Cells, Mice, Frontotemporal Dementia

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Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia

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