The DOI matches its Crossref record; 121 of the 121 references it cites were found in a registry or an index.
Microglial priming in neurodegenerative disease
Abstract
Under physiological conditions, the number and function of microglia--the resident macrophages of the CNS--is tightly controlled by the local microenvironment. In response to neurodegeneration and the accumulation of abnormally folded proteins, however, microglia multiply and adopt an activated state--a process referred to as priming. Studies using preclinical animal models have shown that priming of microglia is driven by changes in their microenvironment and the release of molecules that drive their proliferation. Priming makes the microglia susceptible to a secondary inflammatory stimulus, which can then trigger an exaggerated inflammatory response. The secondary stimulus can arise within the CNS, but in elderly individuals, the secondary stimulus most commonly arises from a systemic disease with an inflammatory component. The concept of microglial priming, and the subsequent exaggerated response of these cells to secondary systemic inflammation, opens the way to treat neurodegenerative diseases by targeting systemic disease or interrupting the signalling pathways that mediate the CNS response to systemic inflammation. Both lifestyle changes and pharmacological therapies could, therefore, provide efficient means to slow down or halt neurodegeneration.
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In the citing paper
“This excessive inflammatory response occurs in many neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's diseases (AD) (Ransohoff, 2016),(Perry and Holmes, 2014),(Burguillos et al., 2011),(Abeliovich and Gitler, 2016), as well as in neurological conditions such as ischemic stroke (Lambertsen et al., 2012),(Burguillos et al., 2015).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Perry and Holmes, 2014
In the citing paper
“The cause of microglial priming is unclear and likely results from multiple factors, including but not limited to (1) a loss of inhibitory ligand–receptor communication with aging neurons (94), (2) interactions with age-related misfolded proteins such as Aβ which promote pro-inflammatory cytokine production (95), (3) age-related exposure to increasing transforming growth factor-β which could”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [94]
In the citing paper
“This state of ‘priming’ is thought to make aged microglia disproportionately reactive to immunological challenges, leading to prolonged neuroinflammation and the cognitive deficits associated with age [65,66].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [66]
In the citing paper
“With aging, microglia take on a 'primed' phenotype, which is characterized by an exaggerated and uncontrolled inflammatory response to an immune stimulus (Perry and Holmes, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Perry and Holmes, 2014
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Barnett, K., Mercer, S. W., Norbury, M., Watt, G., Wyke, S., & Guthrie, B. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60240-2 · Cited by 6,972
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
Self-citationTREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234
Cited by
Sorted by citations
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179
Krasemann, 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
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253
“Microglia are primed in AD brains to be more susceptible to secondary inflammatory insults, resulting in an exacerbated inflammatory response [273].”
BackgroundImmune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952
Metadata
- Authors
- Perry, V. H., & Holmes, C.
- Affiliations
- University of Southampton (GB)
- Corresponding author
- Perry, V. Hugh
- Venue
- Nature Reviews Neurology
- Published
- 2014-03-18
- Volume
- 10
- Issue
- 4
- Pages
- 217-224
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2059996790
- Cited by
- 1,127
- References
- 121
- Citations by year
- 2026: 106 · 2025: 93 · 2024: 86 · 2023: 69 · 2022: 88 · 2021: 97 · 2020: 104 · 2019: 90 · 2018: 119 · 2017: 106 · 2016: 86 · 2015: 65 · 2014: 18
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Wellcome Trust
- National Academy of Sciences of Ukraine
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microglial priming, neurodegeneration, microglial activation, secondary inflammation, systemic inflammation, diabetes mellitus, microglial proliferation, neuroinflammation, neurodegenerative disease treatment, lifestyle intervention
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Brain, Central Nervous System Diseases, Humans, Inflammation, Macrophage Activation, Microglia, Neurodegenerative Diseases
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