The DOI matches its Crossref record; 149 of the 150 references it cites were found in a registry or an index.
Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The combination of NPTX2 (representing synaptic plasticity [35]), NfL (marker for overall neurodegeneration [60, 61]), and GFAP (depicting astrogliosis [62]) reflects the complexity of pathological mechanisms involved in neurodegenerative disorders and FTD in particular [63–66]”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · cited 1×
“Interestingly, secretion of inflammatory proteins such as C1q and IL-1 α by activated microglia leads to activation of astrocytes, which may be neurotoxic in neurodegenerative disorders (64)”
BackgroundRosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · cited 3×
“Many reports have observed decreased C9orf72 transcript levels in tissues from mutation carriers (11, 90).”
BackgroundA Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
Cited by
Sorted by citations
Microglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
“The mechanism by which these repeat expansions may cause disease is outlined in three hypotheses: first, downregulation of gene expression (haploinsufficiency) leads to a loss of C9orf72’s normal cellular function; second, the presence of sense and antisense RNA foci could sequester RNA-binding proteins, resulting in…”
BackgroundLysosomes as a therapeutic target
Bonam, S. R., Wang, F., & Muller, S. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0036-1 · Cited by 786
“Indeed, autoantibodies against ganglio side GM1 and GD1a, sulfoglucuronylparagloboside, neurofilament proteins, FAS/CD95 and voltage gated Ca 2+ channels have all been reported in patients with ALS (reviewed elsewhere 125 ) .”
BackgroundALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?
Mejzini, R., Flynn, L. L., Pitout, I. L., Fletcher, S., Wilton, S. D., & Akkari, P. A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01310 · Cited by 803
TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging
Xu, D., Jin, T., Zhu, H., Chen, H., Ofengeim, D., Zou, C., Mifflin, L., Pan, L., Amin, P., Li, W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.041 · Cited by 461
“Activated microglia are a universal feature of ALS/FTD pathology (Lall and Baloh, 2017).”
Metadata
- 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
- Published
- 2017-07-24
- Volume
- 127
- Issue
- 9
- Pages
- 3250-3258
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
