[Fluorescence analysis of the action of soluble derivatives of fullerene C60 on amyloid fibrils of the brain peptide Abeta(1-42)].

It has been shown by fluorescence analysis in vitro that the water-soluble sodium salt of the polycarboxylic derivative of fullerene C60, fullerenol, and complexes of fullerene C60 with polyvinylpyrrolidone (mol. wt. 25000 and 10000) destroy amyloid fibrils of the brain peptide Abeta(1-42) and prevent their formation. The results of fluorescence analysis confirmed the data obtained earlier by high-resolution electron microscopy. Fluorescence analysis and electron microscopy are complementary methods for the selection of effective antiamylod drugs.

[Effect of nitroderivatives of fullerene C60 on amyloid fibrils of Abeta(1-42) peptide of the brain and muscle X-protein].

The antiamyloidogenic capacity of water-soluble nitroderivatives of fullerene C60: methyl ester of LN-[(2-nitroglyceryl) fullerenyl] proline, methyl ester of LN-[(2,3-dinitroglyceryl) fullerenyl] proline, and 2 nitroxyethyl ether LN-([2-(nitroxy) ethyl] fullerenyl) proline has been studied in vitro by high-resolution electron microscopy. It was shown that these fullerene C60 nitroderivatives are able to prevent the formation of amyloid fibrils by the brain Abeta(1-42)-peptide and muscle X-protein and to destroy mature fibrils. Electron microscopy is a promising method for selecting effective antiamyloidogenic drugs. The antiamyloidogenic activity of nanodimensional fullerene C60 nitroderivatives offers strong possibilities for creating a new nanotechnology for the therapy of amyloidoses.

[Role of light chains of myosin in the regulation of contraction of vertebrate striated muscles].

The data of the study on Ca2+ sensitivity of ATPase activity of myosin from vertebrate striated muscles in the presence of actin and the conditions of its manifestation and disappearance are presented. The role of Ca2+ sensitivity of actin-activated myosin ATPase in the regulation of contraction of vertebrate striated muscles is discussed.

[Effect of fullerenes C60 on the amyloids of X-protein].

The inhibitory effect of hydrated fullerene C60 (HyFn) and the sodium salt of the fullerene polycarboxylic derivative C60Cl (C6H4CH2COONa)5 on the formation of amyloid fibrils by X-protein in vitro has been studied by electron microscopy. It has been shown that these compounds not only destroyed mature amyloid fibrils but also prevented the formation of new fibrils. This property of fullerenes, nanoparticles, can be used for the development of a novel medicinal nanotechnology in the therapy of amyloidoses.

Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task.

It has been shown for the first time by transmission electron microscopy that the hydrated fullerene C60 inhibited the fibrillization of amyloid-beta25-35 peptide. The fullerene affected the amyloid-beta25-35 assembly, manifesting its anti-amyloidogenic capacity. Our in vivo investigations demonstrated also that a single intracerebroventricular injection of the C60 hydrated fullerene at a dose of 7.2 nmol/ventricle significantly improved the performance of the cognitive task in control rats. The intracerebroventricular injection of the C60 hydrated fullerene (3.6 nmol/ventricle) prevented the impairment of performance of the cognitive task induced by amyloid-beta25-35 (22.5 nmol/ventricle). The results obtained may be useful in the development of therapy of Alzheimer's disease.

[Electron microscopic study of the influence of fullerene on the formation of amyloid fibrils by A beta(25-35) peptide].

The anti-amyloidogenic capacity of hydrated fullerene C60 HyFn was revealed by the use of electron microscopy. We first showed that when, connecting with growing amyloid fibrils formed by A beta(25-35)-peptide, fullerene prevented their subsequent growth and interfered with the formation of new fibrils. Instead of long helically twisted ribbons formed by A beta(25-35)-peptide in the absence of fullerene, short narrow protofibrils were found in the presence of fullerene . These results allow one to suppose that fullerene can be useful for the therapy of Alzheimer's disease.

[Cytotoxicity of amyloid fibrils of X-protein].

It is known that amyloid oligomers, protofibrils, and fibrils induce cell death, and antibiotic tetracycline inhibits the fibrillization of beta amyloid peptides and other amyloidogenic proteins and disassembles their pre-formed fibrils. Earlier we have demonstrated that sarcomeric cytoskeletal proteins of the titin family (X-, C-, and H-proteins) are capable to form in vitro amyloid fibrils, and tetracycline effectively destroys these fibrils. Here we show that the viability of polymorphonuclear leukocytes in the presence of X-protein amyloids depends on the concentration of amyloid fibrils of X-protein and the time of incubation. In addition to the disaggregation of X-protein fibrils, tetracycline eliminated the cytotoxic effect of the protein. The antibiotic itself did not show a toxic effect, and the cell viability in its presence even increased. Our results evidence the potential of this approach for evaluating the effectiveness of drugs preventing or treating amyloidoses.

[Sarcomeric proteins of the titin family form amyloids].

It was shown for the first time that skeletal muscle sarcomeric proteins of the titin family (X-, C- and H-proteins) are able to form in vitro amyloid aggregates of different types: granular aggregates, protofibrils, helically twisted ribbons, linear fibrils, and bundles of linear fibrils. Their amyloid nature was confirmed by electron, polarization, and fluorescence microscopy and by spectral methods. As opposed to other amyloidogenic proteins, X-, C-, and H-proteins easily form amyloids under mild conditions close to physiological ones (pH, ionic strength, temperature). Like amyloid fibrils of Abeta-peptide and tau protein in Alzheimer's disease, amyloid aggregates formed by X-, C-, and H-proteins are destroyed by the antibiotic tetracycline. Thus, new proteins-precursors of amyloids and possible participants of amyloidoses in muscles were discovered. Further study of in vitro amyloidogenesis of these proteins would help to find approaches to controlling this process in organs and tissues.