ИСТИНА

Soluble oligomeric β-amyloid peptide (Aβ1-42) is considered responsible for cognitive dysfunctions in Alzheimer's disease patients. An interaction of Aβ1-42 with nicotinic acetylcholine receptors (nAChRs) leads to cognitive function impairment. Earlier it has been shown that the water-soluble variant of human Lynx1 (ws-Lynx1) can compete with Aβ1-42 for binding to nAChRs. This work continues the study of the ws-Lynx1 role in Alzheimer's disease. Incubation of hippocampal brain slices with 200 nM Aβ1-42 for one hour before long-term potentiation (LTP) induction led to a LTP blockade. In contrast, incubation of brain slices in ACSF containing both 200 nM Aβ1-42 and 10 μM ws-Lynx1 showed a restoration of LTP. Exposure to 1 µM Aβ1-42 for 24 hours caused a significant decreased in endogenous Lynx1 gene expression in the cortical primary neurons but not in the hippocampal primary neurons and had no effect on a7 nAChR gene expression in both cases. An increase in Aβ1-42 concentration up to 5 µM confirmed previously obtained results. Co-application of 5 µM Aβ1-42 with 10 μM ws-Lynx1 restored Lynx1 gene expression. To test a possible role of c-Jun N-terminal kinase (JNK) pathway in a drop in Lynx1 gene expression a selective JNK inhibitor SP600125 Aβ1-42 was used. Co-application of 5 µM Aβ1-42 and SP600125 restored Lynx1 gene expression, while SP600125 had no effect on Lynx1 gene expression. This confirms that the ws-Lynx1 can act as a promising drug for Alzheimer's disease treatment. Work was supported by the Russian Science Foundation (project # 16-14-00102).