Pyrrolylquinoxaline-2-one derivative as a potent therapeutic factor for brain trauma rehabilitation

Traumatic brain injury (TBI) often causes massive brain cell death accompanied by the accumulation of toxic factors in interstitial and cerebrospinal fluids. The persistence of the damaged brain area is not transient and may occur within days and weeks. Chaperone Hsp70 is known for its cytoprotective and antiapoptotic activity, and thus, a therapeutic approach based on chemically induced Hsp70 expression may become a promising approach to lower post-traumatic complications. To simulate the processes of secondary damage, we used an animal model of TBI and a cell model based on the cultivation of target cells in the presence of cerebrospinal fluid (CSF) from injured rats. Here we present a novel low molecular weight substance, PQ-29, which induces the synthesis of Hsp70 and empowers the resistance of rat C6 glioma cells to the cytotoxic effect of rat cerebrospinal fluid taken from rats subjected to TBI. In an animal model of TBI, PQ-29 elevated the Hsp70 level in brain cells and significantly slowed the process of the apoptosis in acceptor cells in response to cerebrospinal fluid action. The compound was also shown to rescue the motor function of traumatized rats, thus proving its potential application in rehabilitation therapy after TBI. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Ministry of Education and Science of the Russian Federation, Minobrnauka: 0124-2019-002Russian Foundation for Basic Research, RFBR: 20-33-70102Russian Science Foundation, RSF: 18-74-10087Funding: This research was funded by Russian Science Foundation, research project #18-74-10087 (V.F.L., E.A.D., M.A.M., E.R.M.), Russian Foundation for Basic Research, research project #20-33-70102 (I.A.U., O.N.C., V.N.C, M.?.T., I.V.G.), and by The Ministry of Education and Science of Russian Federation № 0124-2019-002 (R.V.S., N.D.A., B.A.M.)

Dataset of NMR-Spectra Pyrrolyl- and Indolylazines and Evidence of Their Ability to Induce Heat Shock Genes Expression in Human Neurons

These data are related to our previous paper “Synthesis and approbation of new neuroprotective chemicals of pyrrolyl- and indolylazine classes in a cell model of Alzheimer's disease” (Dutysheva et al., 2021), in which we demonstrate neuroprotective abilities of pyrrolyl- and indolylazines in a cell model of Alzheimer's disease. Using a novel procedure of photocatalysis we have synthesized a group of new compounds. The current article presents nuclear magnetic resonance spectra including heteronuclear single quantum coherence spectra of chemicals synthesized by us. The effect of new compounds have on heat shock proteins genes expression in reprogrammed human neurons are presented. We also presented data that verify neuronal phenotype of reprogrammed cells. © 2021Funding: This work was supported by the Russian Foundation for Basic Research [Grant No. 20–33–70102], and by the Russian Science Foundation [grant number 18–74–10087]

Protein Interactome of Amyloid-β as a Therapeutic Target

The amyloid concept of Alzheimer’s disease (AD) assumes the β-amyloid peptide (Aβ) as the main pathogenic factor, which injures neural and other brain cells, causing their malfunction and death. Although Aβ has been documented to exert its cytotoxic effect in a solitary manner, there is much evidence to claim that its toxicity can be modulated by other proteins. The list of such Aβ co-factors or interactors includes tau, APOE, transthyretin, and others. These molecules interact with the peptide and affect the ability of Aβ to form oligomers or aggregates, modulating its toxicity. Thus, the list of potential substances able to reduce the harmful effects of the peptide should include ones that can prevent the pathogenic interactions by specifically binding Aβ and/or its partners. In the present review, we discuss the data on Aβ-based complexes in AD pathogenesis and on the compounds directly targeting Aβ or the destructors of its complexes with other polypeptides