| Autor: |
Bychkov ML; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia., Isaev AB; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.; Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia., Andreev-Andrievskiy AA; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.; Institute for Biomedical Problems of Russian Academy of Sciences, 123007 Moscow, Russia., Petrov K; Arbuzov Institute of Organic and Physical Chemistry, Federal Research Center 'Kazan Scientific Center of the Russian Academy of Sciences', Arbuzov Str., 8, 420088 Kazan, Russia., Paramonov AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia., Kirpichnikov MP; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia., Lyukmanova EN; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.; Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia.; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.; Biological Department, Shenzhen MSU-BIT University, Shenzhen 518172, China. |
| Abstrakt: |
Alzheimer disease (AD) is a widespread neurodegenerative disease characterized by the accumulation of oligomeric toxic forms of β-amyloid (Aβ1-42) and dysfunction of the cholinergic system in the different brain regions. However, the exact mechanisms of AD pathogenesis and the role of the nicotinic acetylcholine receptors (nAChRs) in the disease progression remain unclear. Here, we revealed a decreased expression of a number of the Ly6/uPAR proteins targeting nAChRs in the cerebellum of 2xTg-AD mice (model of early AD) in comparison with non-transgenic mice both at mRNA and protein levels. We showed that co-localization of one of them, - neuromodulator Lynx1, with α7-nAChR was diminished in the vicinity of cerebellar astrocytes of 2xTg-AD mice, while Aβ1-42 co-localization with this receptor present was increased. Moreover, the expression of anti-inflammatory transcription factor KLF4 regulating transcription of the Ly6/uPAR genes was decreased in the cerebellum of 2xTg-AD mice, while expression of inflammatory cytokine TNF-α was increased. Based on these data together with observed astrocyte degeneration in the cerebellum of 2xTg-AD mice, we suggest the mechanism by which expression of the Ly6/uPAR proteins upon Aβ pathology results in dysregulation of the cholinergic system and particularly of α7-nAChR function in the cerebellum. This leads to enhanced neuroinflammation and cerebellar astrocyte degeneration. |
