The cumulative effect of the combined action of miR-101 and curcumin in a liposome on a model of Alzheimer's disease in mononuclear cells.

The leading pathological mechanisms of Alzheimer's disease (AD) are amyloidosis and chronic inflammation. The study of new therapeutic drugs of the corresponding action, in particular miRNAs and curcominoids, as well as methods for their packaging, is topical. The aim of the work was to study the effect of miR-101 + curcumin in a single liposome in a cellular AD model.

Effect of curcumin on accumulation in mononuclear cells and secretion in incubation medium of Аβ(40) and cytokines under local excess of Аβ(42)-homoaggregates.

The aim of the work was to investigate accumulation of endogenous Aβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβ42-aggregates’ toxicity and anti-inflammatory effects of curcumin. Mononuclear cells were isolated in Ficoll-Urografin density gradient from venous blood of healthy donors, resuspended and used for testing of homoaggregates of Aβ42 (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβ40 and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA.

Effect of β-amyloid peptide 42 on the dynamics of expression and formation of Аβ40, IL -1β, TNF α, IL -6, IL -10 by peripheral blood mononuclear cells in vitro and its correction by curcumin.

The toxic effect of Аβ-oligomers accompanies chronic inflammation, with cytokines as main mediators. Therefore, the cytokine link of inflammation becomes a new target on the way to restrain amyloidosis. The aim of the study was the effect of aggregated Аβ42 on the dynamics of expression and formation of endogenous Аβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) by peripheral blood mononuclear cells in vitro and its correction by curcumin.

[Cytokines neuroinflammatory reaction to the action of homoaggregatic and liposomal forms of b-amyloid 1-40 in rats].

An injection model of preclinical stages of Alzheimer's disease has been reproduced in rats. It was accompanied by the decrease in the latent period of conditioned reflex avoidance, increasing levels of endogenous b-amyloid peptide 1-40 and activation of inflammatory cytokines (IL-1b, TNF-a, IL-6, IL-10) in the cerebral cortex, hippocampus and blood serum of experimental animals. We belive that changes identified at the biochemical level are prerequisite to modulate neuronal functions in rats induced by Ab40_Human administration.

[Effect of valproic acid on SMN protein level in peripheral blood mononuclear cells of patients with spinal muscular atrophy and different SMN2 copy numbers].

Objective: Spinal muscular atrophy (SMA) is currently untreatable hereditary disorder caused by few types of mutations in the SMN1 gene and respective lack of gene's product - survival motor neuron protein (SMN). Last decade studies have shown that phenotype of the disorder is substantially influenced by copy numbers of homologous SMN2 gene; also, an ability of valproic acid to increase the level of SMN in vitro and in vivo has been shown. We investigated an effect of valproic acid on SMN level in peripheral blood mononuclear cells derived from patients with SMA and their parents and sought for possible predictors for treatment efficacy.