Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy.
4 affiliations
- 1Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, HeidelbergDE-69120, Germany.
- 2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, KuopioFI-70211, Finland.
- 3School of Pharmacy, University of Eastern Finland, KuopioFI-70211, Finland.
- 4Institute of Pharmacology, Faculty of Medicine, Heidelberg University, HeidelbergDE-69120, Germany.
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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BibTeX
@article{petralla2026altered,
title = {{Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy.}},
author = {Sabrina Petralla and Jooseppi Hyvärinen and Mikko Gynther and Alexey Afonin and Marko Lehtonen and Seppo Auriola and Maria Panayotova and Katja M Kanninen and Gert Fricker and Elena Puris},
journal = {Journal of proteome research},
year = {2026},
month = oct,
doi = {10.1021/acs.jproteome.6c00679},
url = {https://europepmc.org/article/MED/42918131},
note = {CC BY},
}
RIS
TY - JOUR
TI - Altered Membrane Protein Abundance in the Cerebral Cortex of the JNPL3 Mouse Model of Tauopathy.
AU - Sabrina Petralla
AU - Jooseppi Hyvärinen
AU - Mikko Gynther
AU - Alexey Afonin
AU - Marko Lehtonen
AU - Seppo Auriola
AU - Maria Panayotova
AU - Katja M Kanninen
AU - Gert Fricker
AU - Elena Puris
PY - 2026
DA - 2026/10/01
JO - Journal of proteome research
DO - 10.1021/acs.jproteome.6c00679
UR - https://europepmc.org/article/MED/42918131
AB - 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.
SN - 1535-3893
SN - 1535-3907
ER -