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Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases
Lee M, Cho T, Jantaratnotai N, Wang YT, McGeer E, McGeer PL.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010-03-12
Topic: Brain proteins, microglia and lab models
Oxidative stress induced by inhibition of glutathione (GSH) biosynthesis with D,L-buthionine-S,R-sulfoximine (BSO) causes human microglia, human astrocytes, THP-1 cells, and U373 cells to secrete materials toxic to human neuroblastoma SH-SY5Y cells and stimulates them to release TNF-alpha, IL-6, and nitrite ions. The effect is correlated with activation of the inflammatory pathways P38 MAP- kinase, Jun-N-terminal kinase, and NF-kappaB. The effect is reduced by adding to the medium GSH or clotrimazole (CTM), an inhibitor of Ca(2+)-influx through TRPM2 channels.
Key findings
- The effect is correlated with activation of the inflammatory pathways P38 MAP- kinase, Jun-N-terminal kinase, and NF-kappaB.
- The effect is reduced by adding to the medium GSH or clotrimazole (CTM), an inhibitor of Ca(2+)-influx through TRPM2 channels.
- It is also produced by inhibiting TRPM2 protein expression in microglia and astrocytes through introduction of its small inhibitory RNA (siRNA).
- TRPM2 mRNA is expressed by glial cells but not by SH-SY5Y cells.
Why it matters
This laboratory study found that depleting glutathione in human glial cells caused them to release substances toxic to nerve cells and to activate inflammatory pathways, effects that were reduced by glutathione or clotrimazole. This is early cell-based research and does not yet show whether these findings would treat or prevent Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 45/100
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 (FASEB journal : official publication of the Federation of American Societies for Experimental Biology) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (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 | 2010 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 243 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.5 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Patrick L. McGeer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of British Columbia: institution h-index 1,424 (OpenAlex) |
| Multi-centre 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 20228251) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 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
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Lee, M., Cho, T., Jantaratnotai, N., Wang, Y. T., McGeer, E., & McGeer, P. L. (2010). Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.09-149997
Vancouver
Lee M, Cho T, Jantaratnotai N, Wang YT, McGeer E, McGeer PL. Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010. doi:10.1096/fj.09-149997. PMID: 20228251.
BibTeX
@article{lee2010-20228251,
author = {Lee, M. and Cho, T. and Jantaratnotai, N. and Wang, Y. T. and McGeer, E. and McGeer, P. L.},
title = {{Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases}},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2010},
doi = {10.1096/fj.09-149997},
pmid = {20228251},
url = {https://doi.org/10.1096/fj.09-149997}
}
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