Home › Research › Drug development
Active immunotherapy against pathogenic Cis pT231-tau suppresses neurodegeneration in traumatic brain injury mouse models
Masoume Alipour, Majid Tebianian, Nahid Tofigh, Reyhaneh Sadat Taheri, Sayed Alireza Mousavi, Asal Naseri, Amin Ahmadi, Nayla Munawar et al.. Neuropeptides, 2022-09-03
Topic: Disease mechanisms in lab and animal studies
Traumatic brain injury (TBI), characterized by acute neurological impairment, is associated with a higher incidence of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD), whose hallmarks include hyperphosphorylated tau protein. Recently, phosphorylated tau at Thr231 has been shown to exist in two distinct cis and trans conformations. Moreover, targeted elimination of cis P-tau by passive immunotherapy with an appropriate mAb that efficiently suppresses tau-mediated neurodegeneration in severe TBI mouse models has proven to be a useful tool to characterize the neurotoxic role of cis P-tau as an early driver of the tauopathy process after TBI. Here, we investigated whether active immunotherapy can develop sufficient neutralizing antibodies to specifically target and eliminate cis P-tau in the brain of TBI mouse models. First, we explored the therapeutic efficacy of two different vaccines. C57BL/6 J mice were immunized with either cis or trans P-tau conformational peptides plus adjuvant. After rmTBI in mice, we found that cis peptide administration developed a specific Ab that precisely targeted and neutralized cis P-tau, inhibited the development of neuropathology and brain dysfunction, and restored various structural and functional sequelae associated with TBI in chronic phases. In contrast, trans P-tau peptide application not only lacked neuroprotective properties, but also contributed to a number of neuropathological features, including progressive TBI-induced neuroinflammation, widespread tau-mediated neurodegeneration, worsening functional deficits, and brain atrophy. Taken together, our results suggest that active immunotherapy strategies against pathogenic cis P-tau can halt the process of tauopathy and would have profound clinical implications.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Alipour, M., Tebianian, M., Tofigh, N., Taheri, R. S., Mousavi, S. A., Naseri, A., et al. (2022). Active immunotherapy against pathogenic Cis pT231-tau suppresses neurodegeneration in traumatic brain injury mouse models. Neuropeptides. https://doi.org/10.1016/j.npep.2022.102285
Vancouver
Alipour M, Tebianian M, Tofigh N, Taheri RS, Mousavi SA, Naseri A, et al. Active immunotherapy against pathogenic Cis pT231-tau suppresses neurodegeneration in traumatic brain injury mouse models. Neuropeptides. 2022. doi:10.1016/j.npep.2022.102285. PMID: 36087426.
BibTeX
@article{alipour2022-36087426,
author = {Alipour, Masoume and Tebianian, Majid and Tofigh, Nahid and Taheri, Reyhaneh Sadat and Mousavi, Sayed Alireza and Naseri, Asal and Ahmadi, Amin and Munawar, Nayla and others},
title = {{Active immunotherapy against pathogenic Cis pT231-tau suppresses neurodegeneration in traumatic brain injury mouse models}},
journal = {Neuropeptides},
year = {2022},
doi = {10.1016/j.npep.2022.102285},
pmid = {36087426},
url = {https://doi.org/10.1016/j.npep.2022.102285}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Traumatic brain injury (TBI), characterized by acute neurological impairment, is associated with a higher incidence of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD), whose hallmarks include hyperphosphorylated tau protein.
- After rmTBI in mice, we found that cis peptide administration developed a specific Ab that precisely targeted and neutralized cis P-tau, inhibited the development of neuropathology and brain dysfunction, and restored various structural and functional sequelae associated with TBI in chronic phases.
- Taken together, our results suggest that active immunotherapy strategies against pathogenic cis P-tau can halt the process of tauopathy and would have profound clinical implications.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropeptides) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2022 — within 6 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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 | 2 / 2 | Indexed in PubMed (PMID 36087426) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Drug development
Also tagged “phosphorylation”
387 studies in the library carry the topic tag “phosphorylation”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 387 tagged studies.