The DOI matches its Crossref record; 81 of the 81 references it cites were found in a registry or an index.
Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with neuronal cell death that is thought to involve aberrant immune responses. Here we investigated the role of innate immunity in a mouse model of ALS. We found that inflammatory monocytes were activated and that their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We also found a decrease in resident microglia in the spinal cord with disease progression. Prior to disease onset, splenic Ly6Chi monocytes expressed a polarized macrophage phenotype (M1 signature), which included increased levels of chemokine receptor CCR2. As disease onset neared, microglia expressed increased CCL2 and other chemotaxis-associated molecules, which led to the recruitment of monocytes to the CNS by spinal cord-derived microglia. Treatment with anti-Ly6C mAb modulated the Ly6Chi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss, and extended survival. In humans with ALS, the analogous monocytes (CD14+CD16-) exhibited an ALS-specific microRNA inflammatory signature similar to that observed in the ALS mouse model, linking the animal model and the human disease. Thus, the profile of monocytes in ALS patients may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach.
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“we found an increase in CD39−CD11bHi cells which express Ly6C (Fig. 7g) and which represent peripherally infiltrating monocytes9,12.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [12]
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“We previously reported that CD39 is expressed on adult microglia and can distinguish recruited Ly6C+ monocytes from resident microglia12.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [12]
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“peripheral macrophages that infiltrate motor axons during disease progression may also be neurotoxic (152)”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [152]
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“sialoadhesin (SIGLEC1; also known as CD169) is a marker for mature dendritic cells and macrophages in both mice and humans48 and has been proposed as a marker for invading monocyte-derived macrophages in the CNS as it is not expressed in microglia in health or disease49–52.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [49]
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Cites
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
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“It is now known that there are other forms of familial ALS-related mutations such as TDP-43 , FUS , and the newly discovered mutation in a noncoding region of C9ORF72 (79, 80) , which is the most common known genetic cause of fALS (46”
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Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
Self-citationKrasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
Self-citationIdentification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Self-citationMicroglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329
Microglial signatures and their role in health and disease
Butovsky, O., & Weiner, H. L. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0057-5 · Cited by 1,046
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Metadata
- Authors
- Butovsky, O., Siddiqui, S., Gabriely, G., Lanser, A. J., Dake, B., Murugaiyan, G., Doykan, C. E., Wu, P. M., Gali, R. R., Iyer, L. K., Lawson, R., Berry, J., Krichevsky, A. M., Cudkowicz, M. E., & Weiner, H. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Tufts University (US)
- Corresponding author
- Weiner, Howard L.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2012-09-04
- Volume
- 122
- Issue
- 9
- Pages
- 3063-3087
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3428086
- OpenAlex
- W2119656827
- Cited by
- 481
- References
- 81
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 23 · 2023: 32 · 2022: 41 · 2021: 35 · 2020: 46 · 2019: 23 · 2018: 35 · 2017: 47 · 2016: 50 · 2015: 46 · 2014: 42 · 2013: 28 · 2012: 7
- FWCI
- 25.62
- 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
- ALS Association
- Harvard NeuroDiscovery Center
- Brigham and Women's Hospital
- National Institutes of Health
- Center for Neuroscience Research (P30 NS047243)
- National Institute on Aging (AG027437, R01AG027437)
- National Institute of Neurological Disorders and Stroke (P30NS047243, R01NS088137)
- 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
- amyotrophic lateral sclerosis, inflammatory monocytes, microRNA signature, innate immunity, microglia, monocyte recruitment, spinal cord, CCR2, MCP-1, Ly6C, macrophage polarization, neuronal loss, disease biomarkers, therapeutic target
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Antibodies, Monoclonal, Antigens, Ly, Apyrase, Chemotaxis, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Rats, Inbred Lew, Spinal Cord, Spleen, Superoxide Dismutase, Transcription Factors, Antigens, CD, Macrophages, Alveolar, Apoptosis, Microglia, Inflammation Mediators, Oligonucleotide Array Sequence Analysis, RNA Interference, MicroRNAs, Cell Proliferation, Mice, Rats, Gene Regulatory Networks, Metabolic Networks and Pathways, Immunomodulation, Transcriptome
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