Molekuliarnaia biologiia
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Molekuliarnaia biologiia · Nov 2018
Review[Sestrins are Gatekeepers in the Way from Stress to Aging and Disease].
Sestrins belong to a family of evolutionary conserved proteins which are found in the majority of animal species. While invertebrate genomes contain only one sestrin gene, mammalian and other vertebrate genomes comprise three highly homologous genes that encode Sestrin 1, 2 and 3 proteins (Sesn1, Sesn2 and Sesn3). Sestrins are activated in response to a variety of stimuli and trigger metabolic shifts promoting cell survival under stress conditions. ⋯ Activation of sestrins facilitates cell adaptation to stress through stimulation of antioxidant response and autophagy through regulation of the signaling pathways mediated by AMPK and mTOR kinases. These activities are involved in protection of the organism during physical exercise and certain level of sestrins activity contributes to the development of age-related diseases. However, prolonged activation of sestrins under chronic stress may cause negative effects for the organism.
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The discovery of CRISPR/Cas9 brought a hope for having an efficient, reliable, and readily available tool for genome editing. CRISPR/Cas9 is certainly easy to use, while its efficiency and reliability remain the focus of studies. The review describes the general principles of the organization and function of Cas nucleases and a number of important issues to be considered while planning genome editing experiments with CRISPR/Cas9. The issues include evaluation of the efficiency and specificity for Cas9, sgRNA selection, Cas9 variants designed artificially, and use of homologous recombination and nonhomologous end joining in DNA editing.
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Molekuliarnaia biologiia · May 2017
Review[The FUS protein: Physiological functions and a role in amyotrophic lateral sclerosis].
Certain forms of amyotrophic lateral sclerosis (ALS) are associated with an altered compartmentalization of FUS and its aggregation in the cytoplasm of motoneurons. FUS is a DNA/RNA-binding protein that is involved in DNA repair and the regulation of transcription, splicing, RNA transport, and local translation. ⋯ The theories attribute degeneration of motor neurons to either loss or gain of FUS function. The review describes the main physiological functions of FUS and considers evidence for each of the theories of ALS pathogenesis.
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In the modern world acute cerebrovascular accidents (strokes) are one of the most important sociomedical problems due to their high share in the structure of morbidity, invalidization and mortality of the population. The main part of strokes is ischemic stroke (IS). IS is a complex (multifactorial) polygenic disease, i.e. develops as a result of interactions between risk factors and genetic components that determine a joint contribution of the sets of independently acting or interacting polymorphic genes. ⋯ It showed progress in this direction, which can be the starting point for the study of the molecular mechanisms determining the pathophysiology of IS. However to a full solution of the problem of identification of the genetic risk factors applicable for the individual prognosis of predisposition to IS, still very far, mainly due to the low replication of results. The way to solve this problem lies through the study of ethnically homogeneous populations and clinically different forms of IS.
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Despite the advances of modern medicine, malignant glioblastoma cure remains an elusive goal. Both the invasive nature and location in vital areas of the brain make this type of tumors difficult for surgical treatment, while the current adjuvant therapy is not as successful as expected. Frequent recurrence and invasiveness of malignant gliomas is due to resistance of glioma stem cells to conventional radiation and chemotherapy. ⋯ Many of these strains have passed Phase I of clinical trials and demonstrated high safety. Despite the obvious potential of the approach, efficiency of the existing strains is still far from being sufficient for effectively curing the disease and require further improvement. The review summarizes results obtained with the most successful variants of oncolytic viruses that come down to the clinical trials and discusses the prospects for new approaches in virotherapy of malignant gliomas.