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Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models
Tian M, Zhu X, Lei Z, Lu Y, Mo L, Tan J.. Research Square, 2026-08-14
Topic: Disease mechanisms in lab and animal studies
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder for which effective multitarget therapies remain unavailable. Mitochondrial dysfunction and consequent cytoplasmic leakage of mitochondrial DNA (mtDNA) activate the cGAS-STING neuroinflammatory cascade, constituting a critical upstream pathogenic event in AD; however, no therapeutic agent specifically targeting this mtDNA leakage step has been developed. Here we report Taulipro, a co-crystal compound comprising taurine, lithium, and L-proline (molar ratio 1.5:1:1), characterized by ¹H NMR, PXRD, ICP-MS, and DSC. Using Aβ42 oligomer-challenged SH-SY5Y cells and 5×FAD mice (16-week oral gavage), we assessed mitochondrial function, cytoplasmic mtDNA leakage, cGAS–STING pathway activation, Aβ pathology, and neuroinflammatory markers. Taulipro reversed Aβ42-induced mitochondrial dysfunction including ROS accumulation, membrane potential depolarization, mPTP opening, ATP depletion, and Ca²⁺ overload and substantially reduced cytoplasmic mtDNA levels, outperforming equimolar taurine, LiCl, and physical mixture. In 5×FAD mice, Taulipro reduced Aβ plaque burden across the DG, CA3, cortex, and thalamus, suppressed cGAS-STING-TBK1-IRF3 signaling, and attenuated downstream p-NFκB, TNFα, and IL-18, with superior efficacy compared with Li₂CO₃ or taurine monotherapy. These results establish a mechanistic link between mitochondrial mtDNA leakage and cGAS-STING-driven neuroinflammation in AD, and identify Taulipro as a promising multitarget candidate for AD therapy.
Key findings
- In 5×FAD mice, Taulipro reduced Aβ plaque burden across the DG, CA3, cortex, and thalamus, suppressed cGAS-STING-TBK1-IRF3 signaling, and attenuated downstream p-NFκB, TNFα, and IL-18, with superior efficacy compared with Li₂CO₃ or taurine monotherapy.
- These results establish a mechanistic link between mitochondrial mtDNA leakage and cGAS-STING-driven neuroinflammation in AD, and identify Taulipro as a promising multitarget candidate for AD therapy.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Tian, M., Zhu, X., Lei, Z., Lu, Y., Mo, L., & Tan, J. (2026). Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models. Research Square. https://doi.org/10.21203/rs.3.rs-10416296/v1
Vancouver
Tian M, Zhu X, Lei Z, Lu Y, Mo L, Tan J. Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models. Research Square. 2026. doi:10.21203/rs.3.rs-10416296/v1.
BibTeX
@article{tian2026-47e82ed4,
author = {Tian, M. and Zhu, X. and Lei, Z. and Lu, Y. and Mo, L. and Tan, J.},
title = {{Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10416296/v1},
url = {https://doi.org/10.21203/rs.3.rs-10416296/v1}
}
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