The Effect of Ionizing Radiation on Cognitive Functions in Mouse Models of Alzheimer's Disease.

The present study demonstrates the effect of combined ionizing radiation (γ rays, 0.24 Gy, 661.7 keV, whole body and 12C, 0.18 Gy, 450 MeV, head region) on the behavior of animals in mouse transgenic models of Alzheimer's disease. Significant improvement of spatial learning and stimulation of locomotor and exploratory behavior were observed in wild-type mice after irradiation. However, an anxiolytic effect and stimulation of locomotor and exploratory behavior were revealed in irradiated mice with tauopathy. Mice with cerebral amyloidosis also exhibited improved learning in the odor recognition test. No negative effects of irradiation were detected.

Associations between vitamin D-binding protein (DBP) gene polymorphism (TAAA)n and development of osteoporosis in the Volga-Ural region of Russia.

Study of DBP gene (TAAA) n polymorphism in women of postmenopausal age revealed a significantly lower incidence of DBP(*) 10 allele and a higher incidence of DBP(*) 11 allele in Russian women with bone fractures in comparison with the relevant controls (χ(2) = 4.47, p = 0.034 and χ(2) = 4.28, p = 0.038, respectively). Allele DBP(*) 11 is a high risk marker (OR = 1.93; 95%CI 1.06-3.48), while allele DBP(*)10 a marker of low risk of bone fractures (OR = 0.59; 95%CI 0.37-0.94). A trend to a reduction of mineral density of the femoral neck and of the lumbar vertebrae in women with DBP(*) 10(*) 8 genotype of DBP gene polymorphic locus (TAAA) n in comparison with DBP(*) 10(*) 10 and DBP(*) 10(*) 11 genotype carriers is traced.

[Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer's disease].

Recently the studies of Alzheimer's disease have become particularly actual and have attracted scientists from all over the world to this problem as a result of dissemination of this dangerous disorder. The reason for such pathogenesis is not known, but the final image, for the first time obtained on microscopic brain sections from patients with this disease more than a hundred years ago, is well known to clinicists. This is the deposition of Abeta amyloid in the brain tissue of senile plaques and fibrils. Many authors suppose that the deposition of beta-amyloid provokes secondary neuronal changes which are the reason of neuron death. Other authors associate the death of neurons with hyperphosphorylation oftau-proteins which form neurofibrillar coils inside nerve cells and lead to their death. For creation of methods of preclinical diagnostics and effective treatment of Alzheimer's disease novel knowledge is required on the nature of triggering factors of sporadic isoforms of Alzheimer's disease, on cause-effect relationships of phosphorylation of amyloid precursor protein with formation of pathogenic beta-amyloids, on the relationship with these factors of hyperphosphorylation of tau-protein and neuron death. In this review we analyze the papers describing the increasing of intensity of biosynthesis in neurons in normal conditions and under the stress, the possibility of development of energetic unbalanced neurons and activation of their protective systems. Phosphorylation and hyperphosphorylation of tau-proteins is also tightly connected with protective mechanisms of cells and with processes of evacuation of phosphates, adenosine mono-phosphates and pyrophosphates from the region of protein synthesis. Upon long and high intensity of protein synthesis the protective mechanisms are overloaded and the complementarity of metabolitic processes is disturbed. This results in dysfunction of neurons, transport collapse, and neuron death.

[Formation and participation of nano-amyloids in pathogenesis of Alzheimer's disease and other amyloidogenic diseases].

Studies of neurodegenetrative disorders have become particularly actual attracting the attention of researchers from over the world because of the dissemination of Alzheimer's disease. The reason for such pathogenesis is the transition of a "healthy" molecule or peptide from the native conformation into a very stable "pathological" isoform. During this, molecules in the "pathological" conformation aggregate, forming amyloid fibrils that can increase without any control. Novel knowledge is required on sporadic isoforms of Alzheimer's disease, on the nature of triggering mechanisms of conformational transitions of beta-amyloid fragments from normally functioning proteins into new formations--nano-beta-amyloids--that spiral out of control of neurons and organism which leads to the loss of neurons. Herein we review studies devoted to the formation of amyloid fibrils and their role in pathogenesis of amyloid diseases.

[The formation and role of beta-amyloid peptides in neurons upon amyloidosis].

The formation mechanism of amyloid peptides in normally functioning neuron and upon the development of amyloidosis resulting in neuron death is described. Amyloid peptides are formed by enzymatic processing of a large protein precursor and participate in intermolecular interactions after conformational rearrangements resulting in the formation of pathogenic structures. They enter into the cascade of molecular and cellular events leading to amyloidosis and death of nervous cells. These molecular events clarify the relation between the conformation and function of neuropathogenic peptides and the role of this relation in the development of pathology of differentiated neurons. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

[Conformational and intermolecular interactions of proteins in amyloidosis].

A conception on amyloidosis as a key factor of neuronal death in neurodegenerative diseases is stated. Experimental evidence is presented that amyloidosis is caused by alterations in the activity of a number of enzymes as well as conformational changes in pathogenic proteins. Arguments for amyloidosis as the universal biological mechanism of specific elimination of neurons showing changed metabolic and physiological status of cell differentiation are adduced. The final pattern of cell death seems to differ cardinally from that in both apoptosis and necrosis.

Mechanisms of extraribosomal protein biosynthesis in eukaryotes.

The appearance of newly synthesized proteins in the total protein fraction of a cell-free protein-synthesizing system not containing ribosomes and mRNA and enriched with polyenzyme complexes of aminoacyl-tRNA synthetases and corresponding proteins is proved experimentally. For modeling of extraribosomal protein biosynthesis we proposed a molecular polyenzyme mechanism of protein biosynthesis on a protein matrix.

[Isolation and purification of specific proteins, forming during endometrium differentiation into decidual tissue]. / Vydelenie i ochistka spetsificheskikh belkov, obrazuiushchikhsia pri differentsirovke éndometriia v detsidual'nuiu tkan'.

Using analytical PAAG-electrophoresis two specific proteins, D1 and D2, were found in decidual tissue of pregnant women (6-12 weeks). These proteins were isolated and purified by means of ammonium sulfate saturation, chromatography on Sepharose 6B and ion exchange chromatography on DEAE 52 cellulose. The degree of purification of both D1 and D2 proteins was 100% and 81%, respectively. The both proteins were free of DNA, RNA and polysaccharides. The pI values of D1 and D2 proteins were at pH 5.6-6.0. According to gel electrophoresis on PAA-SDS-Na and gel filtration on Sepharose 6B, molecular weight of D1 protein was about 50,000-55,000 and of D2 protein--150,000-160,000 and 300,000-320,000, respectively. The specific decidual proteins D1 and D2 appear to be distinct from the so-called "pregnancy proteins" described previously.

[Comparative gel-electrophoretic study of soluble human endometrial and decidual proteins]. / Sravnitel'noe gel'-élektroforeticheskoe issledovanie rastvorimykh belkov éndometriia i detsidual'noi tkani cheloveka.

As shown by polyacrylamide gel disc electrophoresis, 21 fractions of soluble proteins were found in human endometrium at the proliferative step, whereas the decidual tissue contained only 13 fractions. Two specific protein components D1 and D2 with molecular weight 52,000 and 150,000 daltons, respectively, were observed in the cytosol of decidual tissue. The decrease in quantitative spectrum of soluble proteins from decidual tissue was apparently related to its narrow specialization during the differentiation process.

[Characteristics of testosterone-binding cytoplasmic components in the human endometrium and their interaction with chromatin]. / Kharakteristika komponentov tsitoplazmy endometriia cheloveka, sviazyvaiushchikh testosteron, i ikh vzaimodeistvie s khromatinom

The existence of macromolecules which specifically bind 3H-testosterone is demonstrated in the soluble fraction of human uterus endometrium. Testosterone receptors of endometrial cytosol are heterogenous and comprise the component with high affinity (Kd--2,9x10(-10) M) and low capacity (concentration of binding sites--0,5 pmoles per mg of protein) and the component with lower affinity and higher capacity (4x10(-9) M and 4 pmoles/mg of protein respectively). Incubation of sliced of endometrium at 37 (but not at 0 degrees) with 3H-testosterone results in the binding of the steroid by chromatin. On the other hand, testosterone-cytoplasmic receptor complex is able to associate with chromatin at 0 degrees. Chromatin did not bind free 3H-testosterone under these conditions. The existence of the receptor for testosterone in endometrial cells promoting its transport into the nucleus and binding with chromatin corroborates the previously shown specific action of testosterone on messenger RNA biogenesis in the uterus. Polyinductor model of regulation of gene expression in higher organisms by steroid hormones is discussed.

[Specific binding of progesterone to the proteins of human endometrial cells]. / Spetsificheskoe sviazyvanie progesterona s belkami kletok éndometriia cheloveka

A specific complex of protein-receptor with hormone, which had a sedimentation coefficient 3.8S, was formed in cell nuclei on incubation of endometrial tissue from pregnant woman with 3H-progestrone at 37 degrees C in vitro. In cell cytoplasm of endometrium the progesterone-protein complex was observed which sedimented at 6.8S and 4.2S. Progesterone was accumulated mainly in nuclei; lower concentrations of the hormone were found in cell cytoplasm of endometrium. Fractions of mitochondria, microsomes and ribosomes also bound the hormone but less distinct as compared with the nuclei. The formation of cytoplasmic complex of progesterone with protein-receptor occurred on incubation of endometrial cytoplasmic fraction with 3h-progesterone at 4 degrees C.