Inhibition of sialidase activity as a therapeutic approach

Victor Yu Glanz,1 Veronika A Myasoedova,2 Andrey V Grechko,3 Alexander N Orekhov2,4 1Department of Genetics, Cytology and Bioengineering, Faculty of Biology and Medicine, Voronezh State University, Voronezh, Russia; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russia; 3Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia Abstract: The demand for novel anti-influenza drugs persists, which is highlighted by the recent pandemics of influenza affecting thousands of people across the globe. One of the approaches to block the virus spreading is inhibiting viral sialidase (neuraminidase). This enzyme cleaves the sialic acid link between the newly formed virions and the host cell surface liberating the virions from the cell and maintaining the cycle of infection. Viral neuraminidases appear therefore as attractive therapeutic targets for preventing further spread of influenza infection. Compared to ion channel blockers that were the first approved anti-influenza drugs, neuraminidase inhibitors are well tolerated and target both influenza A and B viruses. Moreover, neuraminidase/sialidase inhibitors may be useful for managing some other human pathologies, such as cancer. In this review, we discuss the available knowledge on neuraminidase or sialidase inhibitors, their design, clinical application, and the current challenges. Keywords: sialidase, neuraminidase, neuraminidase inhibitor, influenza, drug desig

Mitochondrial genome variability: the effect on cellular functional activity

Aleksandrina S Volobueva,1 Alexandra A Melnichenko,2 Andrey V Grechko,3 Alexander N Orekhov2,4 1Laboratory of Gene Therapy, Biocad Biotechnology Company, Saint-Petersburg, Strelnya, Russia; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia; 3Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow, Russia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia Abstract: Mitochondria are the key players in cell metabolism, calcium homeostasis, and reactive oxygen species (ROS) production. Mitochondrial genome alterations are reported to be associated with numerous human disorders affecting nearly all tissues. In this review, we discuss the available information on the involvement of mitochondrial DNA (mtDNA) mutations in cell dysfunction. Keywords: mitochondria, mutation, apoptosis, reactive oxygen species, ATP, electron transfer chai

Role of androgens in cardiovascular pathology

Dimitry A Chistiakov,1 Veronika A Myasoedova,2 Alexandra A Melnichenko,2 Andrey V Grechko,3 Alexander N Orekhov2,4 1Department of Neurochemistry, Division of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center of Psychiatry and Narcology, Moscow, Russia; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russia; 3Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow, Russia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia Abstract: Cardiovascular effects of android hormones in normal and pathological conditions can lead to either positive or negative effects. The reason for this variation is unknown, but may be influenced by gender-specific effects of androids, heterogeneity of the vascular endothelium, differential expression of the androgen receptor in endothelial cells (ECs) and route of androgen administration. Generally, androgenic hormones are beneficial for ECs because these hormones induce nitric oxide production, proliferation, motility, and growth of ECs and inhibit inflammatory activation and induction of procoagulant, and adhesive properties in ECs. This indeed prevents endothelial dysfunction, an essential initial step in the development of vascular pathologies, including atherosclerosis. However, androgens can also activate endothelial production of some vasoconstrictors, which can have detrimental effects on the vascular endothelium. Androgens also activate proliferation, migration, and recruitment of endothelial progenitor cells (EPCs), thereby contributing to vascular repair and restoration of the endothelial layer. In this paper, we consider effects of androgen hormones on EC and EPC function in physiological and pathological conditions. Keywords: cardiovascular disorders, atherosclerosis, androgens, testosterone therapy, risk factor