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MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration
Barker SJ, Raju RM, Milman NEP, Wang J, Davila-Velderrain J, Gunter-Rahman F, Parro CC, Bozzelli PL et al.. Science translational medicine, 2021-11-03
Topic: Brain proteins, microglia and lab models
Recent increases in human longevity have been accompanied by a rise in the incidence of dementia, highlighting the need to preserve cognitive function in an aging population. A small percentage of individuals with pathological hallmarks of neurodegenerative disease are able to maintain normal cognition. Although the molecular mechanisms that govern this neuroprotection remain unknown, individuals that exhibit cognitive resilience (CgR) represent a unique source of therapeutic insight. For both humans and animal models, living in an enriched, cognitively stimulating environment is the most effective known inducer of CgR. To understand potential drivers of this phenomenon, we began by profiling the molecular changes that arise from environmental enrichment in mice, which led to the identification of MEF2 transcription factors (TFs). We next turned to repositories of human clinical and brain transcriptomic data, where we found that the MEF2 transcriptional network was overrepresented among genes that are most predictive of end-stage cognition. Through single-nucleus RNA sequencing of cortical tissue from resilient and nonresilient individuals, we further confirmed up-regulation of MEF2C in resilient individuals to a subpopulation of excitatory neurons. Last, to determine the causal impact of MEF2 on cognition in the context of neurodegeneration, we overexpressed Mef2a/c in the PS19 mouse model of tauopathy and found that this was sufficient to improve cognitive flexibility and reduce hyperexcitability. Overall, our findings reveal a previously unappreciated role for MEF2 TFs in promoting CgR, highlighting their potential as biomarkers or therapeutic targets for neurodegeneration and healthy aging.
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APA 7th
Barker, S. J., Raju, R. M., Milman, N. E. P., Wang, J., Davila-Velderrain, J., Gunter-Rahman, F., et al. (2021). MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration. Science translational medicine. https://doi.org/10.1126/scitranslmed.abd7695
Vancouver
Barker SJ, Raju RM, Milman NEP, Wang J, Davila-Velderrain J, Gunter-Rahman F, et al. MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration. Science translational medicine. 2021. doi:10.1126/scitranslmed.abd7695. PMID: 34731014.
BibTeX
@article{barker2021-34731014,
author = {Barker, S. J. and Raju, R. M. and Milman, N. E. P. and Wang, J. and Davila-Velderrain, J. and Gunter-Rahman, F. and Parro, C. C. and Bozzelli, P. L. and others},
title = {{MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration}},
journal = {Science translational medicine},
year = {2021},
doi = {10.1126/scitranslmed.abd7695},
pmid = {34731014},
url = {https://doi.org/10.1126/scitranslmed.abd7695}
}
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Key findings
- We next turned to repositories of human clinical and brain transcriptomic data, where we found that the MEF2 transcriptional network was overrepresented among genes that are most predictive of end-stage cognition.
- Overall, our findings reveal a previously unappreciated role for MEF2 TFs in promoting CgR, highlighting their potential as biomarkers or therapeutic targets for neurodegeneration and healthy aging.
Study details
- Evidence strengthLow
How this study scored 40/100
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 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science translational medicine) |
| 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 | 2021 — 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 34731014) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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