Dysregulation of Expression of Nicotinic Acetylcholine Receptors and Ly6/uPAR Proteins in the Cingulate Gyrus of the Cerebral Cortex of Patients with Alzheimer's Disease.
8 affiliations
- 1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia.
- 2Psychiatric Clinical Hospital No. 1 named after N. A. Alekseev, Moscow Department of Healthcare, Moscow, 115191 Russia.
- 3Serbsky National Medical Research Center of Psychiatry and Narcology of the Ministry of Health of the Russian Federation, Moscow, 119034 Russia.
- 4Faculty of Psychology, Lomonosov Moscow State University, Moscow, 119234 Russia.
- 5Russian Biotechnology University (Rosbiotech), Moscow, 125080 Russia.
- 6Department of Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.
- 7Moscow Center for Advanced Research, Moscow, 123592 Russia.
- 8Department of Biology, Shenzhen MSU-BIT University, Guangdong Province, Shenzhen, 518172 China.
Abstract
Alzheimer's disease (AD) is a common neurodegenerative disorder associated with the dysfunction of nicotinic acetylcholine receptors (nAChRs). The function of nAChRs is normally regulated by endogenous ligands, such as acetylcholine and three-finger proteins belonging to the Ly6/uPAR family. However, information on the involvement of these proteins in the pathogenesis of AD is lacking. In this study, by using a bioinformatic analysis, we identified increased mRNA levels of Ly6/uPAR proteins (Lynx1, Lynx2, SLURP-1, Ly6G6E, etc.) in the entorhinal, temporal, and frontal cortex in AD patients with neurodegenerative symptoms, as well as an increase in the mRNA level of Ly6E in the hippocampus in patients with asymptomatic AD. Furthermore, in the cortex and cerebellum, we identified multidirectional changes in the mRNA expression of different nAChR subunits and regulators of inflammation (CD59, CD177, Lypd2, Lypd4, and Lypd8) and metabolism (GPIHBP and Ly6D), also belonging to the Ly6/uPAR protein family. By using immunostaining and Western blotting, we confirmed increased protein levels of Lynx1, Lynx2, and the β2 nAChR subunit in the cingulate gyrus adjacent to the entorhinal cortex in patients with AD, as well as decreased protein levels of the α4 and α7 nAChR subunits. These findings point to complex dysregulation of the cholinergic system in the AD brain at the expression levels both of the individual nAChR subtypes and its natural modulators belonging to the Ly6/uPAR family.
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BibTeX
@article{bychkov2026dysregulation,
title = {{Dysregulation of Expression of Nicotinic Acetylcholine Receptors and Ly6/uPAR Proteins in the Cingulate Gyrus of the Cerebral Cortex of Patients with Alzheimer's Disease.}},
author = {M L Bychkov and A G Ochneva and V M Ushakova and A Yu Morozova and Ya A Zorkina and O V Abramova and G P Kostyuk and M P Kirpichnikov and A S Paramonov and E N Lyukmanova},
journal = {Acta naturae},
year = {2026},
month = jul,
doi = {10.32607/actanaturae.27904},
url = {https://europepmc.org/article/MED/42960058},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dysregulation of Expression of Nicotinic Acetylcholine Receptors and Ly6/uPAR Proteins in the Cingulate Gyrus of the Cerebral Cortex of Patients with Alzheimer's Disease.
AU - M L Bychkov
AU - A G Ochneva
AU - V M Ushakova
AU - A Yu Morozova
AU - Ya A Zorkina
AU - O V Abramova
AU - G P Kostyuk
AU - M P Kirpichnikov
AU - A S Paramonov
AU - E N Lyukmanova
PY - 2026
DA - 2026/07/01
JO - Acta naturae
DO - 10.32607/actanaturae.27904
UR - https://europepmc.org/article/MED/42960058
AB - Alzheimer's disease (AD) is a common neurodegenerative disorder associated with the dysfunction of nicotinic acetylcholine receptors (nAChRs). The function of nAChRs is normally regulated by endogenous ligands, such as acetylcholine and three-finger proteins belonging to the Ly6/uPAR family. However, information on the involvement of these proteins in the pathogenesis of AD is lacking. In this study, by using a bioinformatic analysis, we identified increased mRNA levels of Ly6/uPAR proteins (Lynx1, Lynx2, SLURP-1, Ly6G6E, etc.) in the entorhinal, temporal, and frontal cortex in AD patients with neurodegenerative symptoms, as well as an increase in the mRNA level of Ly6E in the hippocampus in patients with asymptomatic AD. Furthermore, in the cortex and cerebellum, we identified multidirectional changes in the mRNA expression of different nAChR subunits and regulators of inflammation (CD59, CD177, Lypd2, Lypd4, and Lypd8) and metabolism (GPIHBP and Ly6D), also belonging to the Ly6/uPAR protein family. By using immunostaining and Western blotting, we confirmed increased protein levels of Lynx1, Lynx2, and the β2 nAChR subunit in the cingulate gyrus adjacent to the entorhinal cortex in patients with AD, as well as decreased protein levels of the α4 and α7 nAChR subunits. These findings point to complex dysregulation of the cholinergic system in the AD brain at the expression levels both of the individual nAChR subtypes and its natural modulators belonging to the Ly6/uPAR family.
SN - 2075-8251
ER -