Ibuprofen modulates inflammatory and autophagy-associated pathways linked to neurodegenerative pathology in APOE-context-dependent cellular models
Jagadeesh Narasimhappagari, Ling Liu, Srinivas Ayyadevara, W. Sue T. Griffin. Journal of Neuroinflammation, 2026-09-09
Topic: Brain proteins, microglia and lab models
The onset and sustenance of Alzheimers and Parkinsons is solely dependent on the driving power of the immune cytokine interleukin-1 beta (IL-1β), arising from neuronal distress and release of sAPPα, which activates microglia for synthesis and release of IL-1β driving synthesis of βAPP, Aβ plaques and synthesis and activation of MAPKp38 for phosphorylation of tau for neurofibrillary tangle formation in Alzheimers and for a-synuclein for formation of Lewy bodies in Parkinsons. As long-term use of Ibuprofen decreases the risk of both diseases, we pitted the power of Ibuprofen against that of the driving power of IL-1β. RT-PCR and Western immunoblotting were used to determine the levels of IL-1β and its downstream mRNAs and proteins in primary neurons, HMC3 cells, T98G stably transformed with APOEε3 or APOEε4 and SH-SY5Y cells expressing Amyloid Precursor Protein (SH-SYFY-APP). ICC was used to determine the autophagy levels in HMC3 cells. Ibuprofen decreased mRNA and protein levels of IL-1β and its downstream proteins, TNFα, βAPP, MAPKp38, MyD88, NFκB, and COX-2, while increasing the gene levels of synaptophysin and autophagy proteins that favor clearance especially in ApoE3 and -4 cells. Our results showing that Ibuprofen decreases the known mechanism of IL-1β to drive the synthesis of each of the aggregates diagnostic of Alzheimers and Parkinsons while simultaneously boosting autophagy for their clearance provides for a vision of one day with Ibuprofen or some more perfect foil these dread diseases may be prevented.
Key findings
- Our results showing that Ibuprofen decreases the known mechanism of IL-1β to drive the synthesis of each of the aggregates diagnostic of Alzheimers and Parkinsons while simultaneously boosting autophagy for their clearance provides for a vision of one day with Ibuprofen or some more perfect foil these dread diseases may be prevented.
Why it matters
In cellular models, ibuprofen decreased IL-1β and downstream proteins while increasing autophagy proteins, especially in APOE3 and APOE4 cells. These results suggest a potential mechanism for ibuprofen's reported risk reduction, but this is early cellular research.
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Study details
- Evidence strengthLow
How this study scored 32/100
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 (Journal of Neuroinflammation) |
| Journal's citation record | 2 / 4 | Journal of Neuroinflammation: journal h-index 216 (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 | 5 / 5 | 2026 — within 1 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author W. Sue T. Griffin: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Arkansas for Medical Sciences: institution h-index 591 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 32 / 100 | — |
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APA 7th
Narasimhappagari, J., Liu, L., Ayyadevara, S., & Griffin, W. S. T. (2026). Ibuprofen modulates inflammatory and autophagy-associated pathways linked to neurodegenerative pathology in APOE-context-dependent cellular models. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-026-04038-0
Vancouver
Narasimhappagari J, Liu L, Ayyadevara S, Griffin WST. Ibuprofen modulates inflammatory and autophagy-associated pathways linked to neurodegenerative pathology in APOE-context-dependent cellular models. Journal of Neuroinflammation. 2026. doi:10.1186/s12974-026-04038-0.
BibTeX
@article{narasimhappagari2026-e38b6498,
author = {Narasimhappagari, Jagadeesh and Liu, Ling and Ayyadevara, Srinivas and Griffin, W. Sue T.},
title = {{Ibuprofen modulates inflammatory and autophagy-associated pathways linked to neurodegenerative pathology in APOE-context-dependent cellular models}},
journal = {Journal of Neuroinflammation},
year = {2026},
doi = {10.1186/s12974-026-04038-0},
url = {https://doi.org/10.1186/s12974-026-04038-0}
}