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TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor
Dewey CM, Cenik B, Sephton CF, Dries DR, Mayer P, Good SK, Johnson BA, Herz J et al.. Molecular and cellular biology, 2010-12-20
Topic: Brain proteins, microglia and lab models
TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. In this study, we establish sorbitol as a novel physiological stressor that directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We quantify the association of TDP-43 with stress granules over time and show that stress granule association and size are dependent on the glycine-rich region of TDP-43, which harbors the majority of pathogenic mutations. Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules, and is incorporated into stress granules earlier, than wild-type TDP-43; in striking contrast, wild-type TDP-43 forms more stress granules over time, but the granule size remains relatively unchanged. We propose that mutant TDP-43 alters stress granule dynamics, which may contribute to the progression of TDP-43 proteinopathies.
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APA 7th
Dewey, C. M., Cenik, B., Sephton, C. F., Dries, D. R., Mayer, P., Good, S. K., et al. (2011). TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor. Molecular and cellular biology. https://doi.org/10.1128/mcb.01279-10
Vancouver
Dewey CM, Cenik B, Sephton CF, Dries DR, Mayer P, Good SK, et al. TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor. Molecular and cellular biology. 2011. doi:10.1128/mcb.01279-10. PMID: 21173160.
BibTeX
@article{dewey2011-21173160,
author = {Dewey, C. M. and Cenik, B. and Sephton, C. F. and Dries, D. R. and Mayer, P. and Good, S. K. and Johnson, B. A. and Herz, J. and others},
title = {{TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor}},
journal = {Molecular and cellular biology},
year = {2011},
doi = {10.1128/mcb.01279-10},
pmid = {21173160},
url = {https://doi.org/10.1128/mcb.01279-10}
}
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Key findings
- Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress.
- Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules, and is incorporated into stress granules earlier, than wild-type TDP-43; in striking contrast, wild-type TDP-43 forms more stress granules over time, but the granule size remains relatively unchanged.
Why it matters
In cultured cells, sorbitol stress sent TDP-43 into stress granules, and mutant TDP-43 formed larger granules and entered them earlier than wild-type TDP-43. This is cell-culture work on a possible disease mechanism, not a treatment or prevention study.
Study details
- Evidence strengthLow
How this study scored 47/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular biology) |
| Journal's citation record | 3 / 4 | Molecular and Cellular Biology: journal h-index 458 (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 | 1 / 5 | 2011 — within 20 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 | 6 / 7 | Cited 365 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 62 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Gang Yu: h-index 46 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Texas Southwestern Medical Center: institution h-index 1,356 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21173160) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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