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Stress granules and neurodegeneration
Wolozin B, Ivanov P.. Nature reviews. Neuroscience, 2019-10-03
Topic: Brain proteins, microglia and lab models
Recent advances suggest that the response of RNA metabolism to stress has an important role in the pathophysiology of neurodegenerative diseases, particularly amyotrophic lateral sclerosis, frontotemporal dementias and Alzheimer disease. RNA-binding proteins (RBPs) control the utilization of mRNA during stress, in part through the formation of membraneless organelles termed stress granules (SGs). These structures form through a process of liquid-liquid phase separation. Multiple biochemical pathways regulate SG biology. The major signalling pathways regulating SG formation include the mammalian target of rapamycin (mTOR)-eukaryotic translation initiation factor 4F (eIF4F) and eIF2α pathways, whereas the pathways regulating SG dispersion and removal are mediated by valosin-containing protein and the autolysosomal cascade. Post-translational modifications of RBPs also strongly contribute to the regulation of SGs. Evidence indicates that SGs are supposed to be transient structures, but the chronic stresses associated with ageing lead to chronic, persistent SGs that appear to act as a nidus for the aggregation of disease-related proteins. We suggest a model describing how intrinsic vulnerabilities within the cellular RNA metabolism might lead to the pathological aggregation of RBPs when SGs become persistent. This process might accelerate the pathophysiology of many neurodegenerative diseases and myopathies, and it suggests new targets for disease intervention.
Key findings
- Recent advances suggest that the response of RNA metabolism to stress has an important role in the pathophysiology of neurodegenerative diseases, particularly amyotrophic lateral sclerosis, frontotemporal dementias and Alzheimer disease.
- Evidence indicates that SGs are supposed to be transient structures, but the chronic stresses associated with ageing lead to chronic, persistent SGs that appear to act as a nidus for the aggregation of disease-related proteins.
Why it matters
This review suggests that chronic stress granules, which normally are temporary, may become persistent with ageing and act as a starting point for the clumping of disease-related proteins in ALS, frontotemporal dementias, and Alzheimer's disease. It proposes a model for how problems in RNA metabolism might lead to nerve damage, but it does not test a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Neuroscience) |
| Journal's citation record | 4 / 4 | Nature reviews. Neuroscience: journal h-index 572 (OpenAlex, 2026-10-29) |
| 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 | 2 / 5 | 2019 — within 10 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 786 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 87.3 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 5.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 4 / 4 | Cited 366 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pavel V. Ivanov: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31582840) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Wolozin, B., & Ivanov, P. (2019). Stress granules and neurodegeneration. Nature reviews. Neuroscience. https://doi.org/10.1038/s41583-019-0222-5
Vancouver
Wolozin B, Ivanov P. Stress granules and neurodegeneration. Nature reviews. Neuroscience. 2019. doi:10.1038/s41583-019-0222-5. PMID: 31582840.
BibTeX
@article{wolozin2019-31582840,
author = {Wolozin, B. and Ivanov, P.},
title = {{Stress granules and neurodegeneration}},
journal = {Nature reviews. Neuroscience},
year = {2019},
doi = {10.1038/s41583-019-0222-5},
pmid = {31582840},
url = {https://doi.org/10.1038/s41583-019-0222-5}
}
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