[Social cognitive function in neurodegenerative diseases]. / Sotsial'nye kognitivnye funktsii pri neirodegenerativnykh zabolevaniiakh.

The ability to perceive, analyze people's mental states, intentions, thoughts and feelings is an important cognitive function for normal social behavior and interaction. Over the past decade, more attention has been paid to studying how behavioral disorders in patients with neurodegenerative diseases may be explained by theory of mind deficit and whether it can be useful for differential diagnosis. The authors consider the issues of neuroanatomy, neurophysiology of a special kind of cognitive functions provided normal social interaction and interpersonal relationship, problems of its determining in neurodegenerative diseases.

[Heterogeneity of excessive daytime sleepiness in Parkinson's disease]. / Geterogennost' dnevnoi sonlivosti pri bolezni Parkinsona.

For the recent years, a special attention is given to the non-motor symptoms of Parkinson's disease, including sleep/wake disorders representing one of the leading symptoms. Daytime sleepiness occurs in 30-55% of patients depending on duration and stage of the disease, leading to severe maladjustment. This symptom seems to be multifactorial by nature and identification of it's causes could have a great importance for the therapy. The main factors of the development of daytime sleepiness in Parkinson's disease and key points of the pathogenesis of «primary¼ daytime sleepiness are discussed. Diagnostic methods and treatment opportunities are considered as well.

[A role of the MAO-B inhibitor rasagiline in treatment of Parkinson's disease]. / Rol' ingibitora mao-v razagilina v lechenii bolezni Parkinsona.

The current medications for Parkinson's disease (PD) treatment have predominantly symptomatic action. They reduce the severity of main motor symptoms and delay the disability and fatal outcome but do not able to prevent the late stages characterized by multiple motor and non-motor disorders. A search for new drugs, which are able to slow disease progression at the early stage and promote effective treatment of symptoms at the late stage, is extremely urgent. Rasagiline (azilect), a new generation MAO-B inhibitor, helps to solve the problems at different stages of PD.

DNA duplexes containing altered sugar residues as probes of EcoRII and MvaI endonuclease interactions with sugar-phosphate backbone.

Oligonucleotides containing 1-(beta-D-2'-deoxy-threo-pentofuranosyl)cytosine (dCx) and/or 1-(beta-D-2'-deoxy-threo-pentofuranosyl)thymine (dTx) in place of dC and dT residues in the EcoRII and MvaI recognition site CC(A/T)GG were synthesized in order to investigate specific recognition of the DNA sugar-phosphate backbone by EcoRII and MvaI restriction endonucleases. In 2'-deoxyxylosyl moieties of dCx and dTx, 3'-hydroxyl groups were inverted, which perturbs the related individual phosphates. Introduction of a single 2'-deoxyxylosyl moiety into a dC x dG pair resulted in a minor destabilization of double-stranded DNA structure. In the case of a dA x dT pair the effect of a 2'-deoxyxylose incorporation was much more pronounced. Multiple dCx modifications and their combination with dTx did not enhance the destabilization effect. Hydrolysis of dCx-containing DNA duplexes by EcoRII endonuclease was blocked and binding affinity was strongly depended on the location of an altered sugar. A DNA duplex containing a dTx residue was cleaved by the enzyme, but kcat/K(M) was slightly reduced. In contrast, MvaI endonuclease efficiently cleaved both types of sugar-altered substrate analogs. However it did not cleave conformationally perturbed scissile bonds, when the corresponding unmodified bonds were perfectly hydrolyzed in the same DNA duplexes. Based on these data the possible contributions of individual phosphates in the recognition site to substrate recognition and catalysis by EcoRII were proposed. We observed strikingly non-equivalent inputs for different phosphates with respect to their effect on EcoRII-DNA complex formation.

EcoRII endonuclease has two identical DNA-binding sites and cleaves one of two co-ordinated recognition sites in one catalytic event.

EcoRII is a typical restriction enzyme that cleaves DNA using a two-site mechanism. EcoRII endonuclease is unable to cleave DNA which contains a small number of EcoRII recognition sites but the enzyme activity can be stimulated in the presence of DNA with a high frequency of EcoRII sites. To investigate the mechanism of activation, the kinetics of stimulated EcoRII cleavage has been studied. A 14 bp substrate activated the cleavage of the 71 bp substrate, containing one EcoRII recognition site (trans-activation) by a competitive mechanism: the activator increased substrate binding but not catalysis. The activation increased if the substrate concentration decreased and if the activator had a lower affinity for the enzyme than the substrate. The introduction of the second recognition site into the 71 bp duplex also enabled cleavage of this substrate (cis-activation). Pyrophosphate bonds were incorporated into one of two recognition sites to switch off the cleavage of the phosphodiester bonds. Analysis of cleavage products of these modified substrates showed that EcoRII cuts one of two coordinated recognition sites in one catalytic event.