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Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer's disease
McKee CG, Hoffos M, Vecchiarelli HA, Tremblay MÈ.. Frontiers in pharmacology, 2023-02-09
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
As individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive functions and to transitions toward mild cognitive impairment (MCI) and Alzheimer's disease (AD). As microglia possess receptors for communicating with the CNS environment, pharmacological therapies targeting these pathways hold potential for promoting homeostatic microglial functions within the aging CNS. Preclinical and early phase clinical trials investigating the therapeutic effects of pharmacological agents acting on microglia, including reactive oxygen species, TREM2, fractalkine signaling, the complement cascade, and the NLRP3 inflammasome, are currently underway; however, important questions remain unanswered. Current challenges include target selectivity, as many of the signaling pathways are expressed in other cell types. Furthermore, microglia are a heterogenous cell population with transcriptomic, proteomic, and microscopy studies revealing distinct microglial states, whose activities and abundance shift across the lifespan. For example, homeostatic microglia can transform into pathological states characterized by markers of oxidative stress. Selective pharmacological targeting aimed at limiting transitions to pathological states or promoting homeostatic or protective states, could help to avoid potentially harmful off-target effects on beneficial states or other cell types. In this mini-review we cover current microglial pathways of interest for the prevention and treatment of age-related cognitive decline and CNS disorders of aging focusing on MCI and AD. We also discuss the heterogeneity of microglia described in these conditions and how pharmacological agents could target specific microglial states.
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APA 7th
McKee, C. G., Hoffos, M., Vecchiarelli, H. A., & MÈ, T. (2023). Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer's disease. Frontiers in pharmacology. https://doi.org/10.3389/fphar.2023.1125982
Vancouver
McKee CG, Hoffos M, Vecchiarelli HA, MÈ T. Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer's disease. Frontiers in pharmacology. 2023. doi:10.3389/fphar.2023.1125982. PMID: 36969855.
BibTeX
@article{mckee2023-36969855,
author = {McKee, C. G. and Hoffos, M. and Vecchiarelli, H. A. and MÈ, Tremblay},
title = {{Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer's disease}},
journal = {Frontiers in pharmacology},
year = {2023},
doi = {10.3389/fphar.2023.1125982},
pmid = {36969855},
url = {https://doi.org/10.3389/fphar.2023.1125982}
}
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Key findings
- Furthermore, microglia are a heterogenous cell population with transcriptomic, proteomic, and microscopy studies revealing distinct microglial states, whose activities and abundance shift across the lifespan.
- For example, homeostatic microglia can transform into pathological states characterized by markers of oxidative stress.
- Selective pharmacological targeting aimed at limiting transitions to pathological states or promoting homeostatic or protective states, could help to avoid potentially harmful off-target effects on beneficial states or other cell types.
- In this mini-review we cover current microglial pathways of interest for the prevention and treatment of age-related cognitive decline and CNS disorders of aging focusing on MCI and AD.
- We also discuss the heterogeneity of microglia described in these conditions and how pharmacological agents could target specific microglial states.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in pharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36969855) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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