[Proteinopathies--forms of neurodegenerative disorders with protein aggregation-based pathology].

A number of neurodegenerative disorders have recently been coalesced into a group of proteinopathies because of the similarity of molecular mechanisms underlying their pathogenesis. A key step in the development of proteinopathies is a structural change that triggers aggregation of proteins, which are intrinsically prone to form aggregates due to their physical and chemical properties. Present review is devoted to the recent progress in the field of proteinopathies with specific focus on properties of aggregate-prone proteins, main stages of the development of molecular pathology and the role of cellular clearance systems in progression of neurodegeneration. Recent modifications in the nomenclature of neurodegenerative diseases will also be addressed.

[Thermodynamics of calmodulin and tubulin binding to the vinca-alkaloid vinorelbine].

Vinca-alkaloids, such as vinblastine, and some of their derivatives, as for example vinorelbine, are widely used in clinical therapy of leukemia and several types of tumors. Their effects are associated with the disfunctioning of the mitotic spindle, which leads to mitosis blockage and a shutdown of the cell cycle. Their primary target is tubulin, however recent research has shown that some of the vinca-alkaloids inhibit calmodulin binding to its targets. Vinka-alkaloids binding with other proteins could be responsible for their efficiency and neuroprotection. Here we investigated the thermodynamics of vinorelbine interactions with calmodulin and tubulin. It was determined that unlike the other vinca-alkaloids both vinorelbine binding sites are located in the C-domain of calmodulin, and characterized by association constants of 4.0 x 10(5) and 5.4 x 10(4) M(-1). At the same time the thermodynamics of vinorelbine binding to tubulin are not much different from that of other vinca-alkaloids. These results will allow getting a better insight on the reaction mechanisms of vinca-alkaloids on a secondary protein target.

[Thermodynamics of zinc binding to human S100A2].

The regulatory protein S100A2 is localized in the cell nucleus and takes part in the regulation of the cell cycle and cancerogenesis. It belongs to a large family of S100 proteins and can simultaneously bind calcium and zinc ions. Using a direct thermodynamical method of isothermal titration calorimetry we have determined that in the absence of calcium ions the S100A2 protein can bind three zinc ions per each monomer. Besides that it was determined that the thermodynamics of zinc binding to different binding sites on the S100A2 are significantly different. Zinc binding to the first two sites on the S100A2 is enthalpically unfavorable and is driven only by entropic factors, while the binding of the third zinc ion is enthalpically favorable. Analysis of the zinc ion adsorption isotherms shows that their binding occurs in a consecutive order.

[Effect of isomerization of aspartate-7 on the binding of copper (II) ion by the beta-amyloid peptide].

It has been shown for the first time by the method of isothermal calorimetry of titration that the N-terminal amino group of the beta-amyloid protein, which plays a key role in the binding of copper ion, ceases to form the proper coordinating bond as a result of the isomerization of aspartate-7.

[A replaceable nonfrictional membrane filter for the prevention of cell culture contamination]. / Smennyi nefriktsionnyi membrannyi fil'tr dlia predotvrashcheniia kontaminatsii keltiochnykh kul'tur.

A changeable membrane filter preventing the friction between moving parts and the membrane during tight screwing of a culture flask is proposed.