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RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons
van der Linden RJ, Gerritsen JS, Liao M, Widomska J, Pearse RV, White FM, Franke B, Young-Pearse TL et al.. Progress in neurobiology, 2022-07-14
Topic: Brain proteins, microglia and lab models
The RNA binding protein ELAVL4/HuD regulates the translation and splicing of multiple Alzheimer's disease (AD) candidate genes. We generated ELAVL4 knockout (KO) human induced pluripotent stem cell-derived neurons to study the effect that ELAVL4 has on AD-related cellular phenotypes. ELAVL4 KO significantly increased the levels of specific APP isoforms and intracellular phosphorylated tau, molecular changes that are related to the pathological hallmarks of AD. Overexpression of ELAVL4 in wild-type neurons and rescue experiments in ELAVL4 KO cells showed opposite effects and also led to a reduction of the extracellular amyloid-beta (Aβ)42/40 ratio. All these observations were made in familial AD (fAD) and fAD-corrected neurons. To gain insight into the molecular cascades involved in neuronal ELAVL4 signaling, we conducted pathway and upstream regulator analyses of transcriptomic and proteomic data from the generated neurons. These analyses revealed that ELAVL4 affects multiple biological pathways linked to AD, including those involved in synaptic function, as well as gene expression downstream of APP and tau signaling. The analyses also suggest that ELAVL4 expression is regulated by insulin receptor-FOXO1 signaling in neurons. Taken together, ELAVL4 expression ameliorates AD-related molecular changes in neurons and affects multiple synaptic pathways, making it a promising target for novel drug development.
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APA 7th
van der Linden, R. J., Gerritsen, J. S., Liao, M., Widomska, J., Pearse, R. V., White, F. M., et al. (2022). RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons. Progress in neurobiology. https://doi.org/10.1016/j.pneurobio.2022.102316
Vancouver
van der Linden RJ, Gerritsen JS, Liao M, Widomska J, Pearse RV, White FM, et al. RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons. Progress in neurobiology. 2022. doi:10.1016/j.pneurobio.2022.102316. PMID: 35843356.
BibTeX
@article{vanderlinden2022-35843356,
author = {van der Linden, R. J. and Gerritsen, J. S. and Liao, M. and Widomska, J. and Pearse, R. V. and White, F. M. and Franke, B. and Young-Pearse, T. L. and others},
title = {{RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons}},
journal = {Progress in neurobiology},
year = {2022},
doi = {10.1016/j.pneurobio.2022.102316},
pmid = {35843356},
url = {https://doi.org/10.1016/j.pneurobio.2022.102316}
}
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Key findings
- ELAVL4 KO significantly increased the levels of specific APP isoforms and intracellular phosphorylated tau, molecular changes that are related to the pathological hallmarks of AD.
- These analyses revealed that ELAVL4 affects multiple biological pathways linked to AD, including those involved in synaptic function, as well as gene expression downstream of APP and tau signaling.
- The analyses also suggest that ELAVL4 expression is regulated by insulin receptor-FOXO1 signaling in neurons.
- Taken together, ELAVL4 expression ameliorates AD-related molecular changes in neurons and affects multiple synaptic pathways, making it a promising target for novel drug development.
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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 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 (Progress in neurobiology) |
| 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 | 2022 — 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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| 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 35843356) |
| 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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