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Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy
Sabrina Petralla, Jooseppi Hyvärinen, Mikko Gynther, Alexey Afonin, Marko Lehtonen, Seppo Auriola, Maria Panayotova, Katja M. Kanninen et al.. Journal of Proteome Research, 2026-09-16
Topic: Brain proteins, microglia and lab models
Abstract Developing effective therapeutic approaches for tau-associated neurodegenerative diseases, including frontotemporal dementia and Alzheimer’s disease, remains extremely challenging due to their complex pathogeneses. Membrane proteins constitute a large proportion of current therapeutic and drug delivery targets because of their key roles in essential cellular processes. Here, we examined alterations in membrane protein abundances in the prefrontal cortex of male and female mouse models of human tauopathy, JNPL3 mice, compared with sex-matched wild-type (WT) mice using quantitative proteomics. The data-independent acquisition (DIA) proteomics analysis revealed various alterations in membrane proteins involved in different altered pathways in male JNPL3 mice (e.g., nucleotide metabolism and translation) and female JNPL3 mice (e.g., mitochondrial function). In addition, we found sex-associated changes in the abundances of several proteins previously reported to be involved in tau pathology, such as Reelin, DARPP-32, Zyxin, Tbce, and Gng5, in JNPL3 mice. Our multiple-reaction monitoring absolute quantitative analysis of transporter proteins revealed reduced abundance of the main drug efflux transporter ABCB1 in male JNPL3 mice compared with WT animals, with no changes in female groups. All in all, we provide novel information on membrane proteomic changes in male and female mouse models of human tauopathy, JNPL3 mice, which could aid in developing treatments for tau-associated neurodegenerative diseases and facilitate the prediction of neuropharmacokinetics in female and male patients.
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APA 7th
Petralla, S., Hyvärinen, J., Gynther, M., Afonin, A., Lehtonen, M., Auriola, S., et al. (2026). Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy. Journal of Proteome Research. https://doi.org/10.1021/acs.jproteome.6c00679
Vancouver
Petralla S, Hyvärinen J, Gynther M, Afonin A, Lehtonen M, Auriola S, et al. Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy. Journal of Proteome Research. 2026. doi:10.1021/acs.jproteome.6c00679.
BibTeX
@article{petralla2026-e6cc30a0,
author = {Petralla, Sabrina and Hyvärinen, Jooseppi and Gynther, Mikko and Afonin, Alexey and Lehtonen, Marko and Auriola, Seppo and Panayotova, Maria and Kanninen, Katja M. and others},
title = {{Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy}},
journal = {Journal of Proteome Research},
year = {2026},
doi = {10.1021/acs.jproteome.6c00679},
url = {https://doi.org/10.1021/acs.jproteome.6c00679}
}
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Key findings
- Here, we examined alterations in membrane protein abundances in the prefrontal cortex of male and female mouse models of human tauopathy, JNPL3 mice, compared with sex-matched wild-type (WT) mice using quantitative proteomics.
- The data-independent acquisition (DIA) proteomics analysis revealed various alterations in membrane proteins involved in different altered pathways in male JNPL3 mice (e.g., nucleotide metabolism and translation) and female JNPL3 mice (e.g., mitochondrial function).
- In addition, we found sex-associated changes in the abundances of several proteins previously reported to be involved in tau pathology, such as Reelin, DARPP-32, Zyxin, Tbce, and Gng5, in JNPL3 mice.
- Our multiple-reaction monitoring absolute quantitative analysis of transporter proteins revealed reduced abundance of the main drug efflux transporter ABCB1 in male JNPL3 mice compared with WT animals, with no changes in female groups.
Why it matters
In JNPL3 tauopathy mice, proteomics revealed altered membrane protein abundance in the prefrontal cortex, differing between males and females, including reduced levels of the drug efflux transporter ABCB1 in males. This is animal tissue analysis and identifies no treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 31/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Proteome Research) |
| Journal's citation record | 2 / 4 | Journal of Proteome Research: journal h-index 221 (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 | 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 | 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 | 1 / 4 | Last-listed author Elena Puris: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Heidelberg University: institution h-index 1,344 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
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