Репозиторий Университета

© 2019 Elsevier Inc. Loss of dopaminergic neurons in the substantia nigra is one of the pathogenic hallmarks of Parkinson's disease, yet the underlying molecular mechanisms remain enigmatic. While aberrant redox metabolism strongly associated with iron dysregulation and accumulation of dysfunctional mitochondria is considered as one of the major contributors to neurodegeneration and death of dopaminergic cells, the specific anomalies in the molecular machinery and pathways leading to the PD development and progression have not been identified. The high efficiency and relative simplicity of a new genome editing tool, CRISPR/Cas9, make its applications attractive for deciphering molecular changes driving PD-related impairments of redox metabolism and lipid peroxidation in relation to mishandling of iron, aggregation and oligomerization of alpha-synuclein and mitochondrial injury as well as in mechanisms of mitophagy and programs of regulated cell death (apoptosis and ferroptosis). These insights into the mechanisms of PD pathology may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9.

© 2018, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved. Mechanical ventilation is associated with a number of complications that increase the cost of treatment and the hospital mortality rate. In 2004, the term «ventilator-induced diaphragm dysfunction» (VIDD) was proposed to explain one of the reasons for the failure of respiratory support. At present, this term is understood as a combination of atrophy and weakness of the contractile function of the diaphragm caused directly by a long-term mechanical lung ventilation. Oxidative stress, proteolysis, mitochondrial dysfunction, as well as passive overdistension of the diaphragm fibers contribute greatly to the pathogenesis of VIDD. Since 30—80% of patients in the ICU require mechanical respiratory support and even 6—8 hours of mechanical lung ventilation can contribute to the development of a significant weakness of the diaphragm, it can be concluded that the VIDD is an extremely urgent problem in most patients. Its typical clinical presentation is characterized by impaired breathing mechanics and unsuccessful attempts to switch the patient to the spontaneous breathing in the absence of other valid reasons for respiratory disorders. The sonography is the most informative and accessible diagnostic method, and preservation of spontaneous breathing activity and the use of the latest mechanical ventilation modes are considered a promising approach to prevention and correction of the disorders. The search for an optimal strategy for lung ventilation, development of diagnostic and physiotherapeutic methods, as well as the consolidation of the work of a multidisciplinary team of specialists (anesthesiologists and intensive care specialists, neurologists, pulmonologists, surgeons, etc.) can help in solving this serious problem. A review of 122 sources about the VIDD presented data on the background of the issue, the definition of the problem, etiology and pathogenesis, clinical manifestations, methods of diagnosis, the effect of drugs, prevention and therapy.