Механизмы повреждения и защиты клетки при ишемии/реперфузии и экспериментальное обоснование применения препаратов на основе лития в анестезиологии

Pharmaceuticals based on lithium ions have been already used in clinical practice for over 60 years for the treatment of bipolar disorders and remain a basic pharmacological therapy for patients with this disease. In spite of this, the therapeutic mechanisms of action of lithium ions have not been fully investigated. In the past decade, in vitro and in vivo experiments have provided a good deal of data suggesting that lithium ions have previously undescribed neuro-, cardio-, and nephro-protective properties. Numerous investigations have demonstrated that glycogen synthase kinase-3/3, the key enzyme of different pathological and protective signaling pathways, is the target of lithium ions in displaying these effects. This review deals with just these new properties of lithium ions, which make them utterly promising for clinical use in circulatory arrest-associated conditions, which is particularly relevant for anesthesiology and resuscitation. Key words: lithium ions, brain, heart, kidney, postresuscitation disease.Фармакологические препараты на основе ионов лития уже более 60 лет используются в клинической практике для лечения биполярных расстройств и остаются основой фармакотерапии пациентов с этой группой заболеваний. Несмотря на это, терапевтические механизмы действия ионов лития изучены не в полной мере. В течение последних 10 лет в экспериментах in vitro и in vivo было получено множество данных, свидетельствующих о наличии у ионов лития ранее не описанных нейро-, кардио- и нефропротекторных свойств. Основной мишенью ионов лития при реализации этих эффектов является киназа гликогенсинтазы-3в, ключевой фермент различных патологических и защитных сигнальных путей. Данный обзор посвящен новым свойствам ионов лития, делающих их чрезвычайно перспективными для клинического применения при состояниях, связанных с остановкой кровообращения, что особенно актуально для анестезиологии и реаниматологии. Ключевые слова: ионы лития, мозг, сердце, почка, постреанимационная болезнь

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

Mitochondrial abnormalities have been identified as a central mechanism in multiple neurodegenerative diseases and, therefore, the mitochondria have been explored as a therapeutic target. This review will focus on the evidence for mitochondrial abnormalities in the two most common neurodegenerative diseases, Parkinson's disease and Alzheimer's disease. In addition, we discuss the main strategies which have been explored in these diseases to target the mitochondria for therapeutic purposes, focusing on mitochondrially targeted antioxidants, peptides, modulators of mitochondrial dynamics and phenotypic screening outcomes

Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury

Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies

Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles

Extracellular vesicles (EVs) are small biological structures that are released by cells and have important roles in intercellular communication [...

Marine natural products from the russian pacific as sources of drugs for neurodegenerative diseases

Neurodegenerative diseases are growing to become one of humanity’s biggest health problems, given the number of individuals affected by them. They cause enough mortalities and severe economic impact to rival cancers and infections. With the current diversity of pathophysiological mechanisms involved in neurodegenerative diseases, on the one hand, and scarcity of efficient prevention and treatment strategies, on the other, all possible sources for novel drug discovery must be employed. Marine pharmacology represents a relatively uncharted territory to seek promising compounds, despite the enormous chemodiversity it offers. The current work discusses one vast marine region—the Northwestern or Russian Pacific—as the treasure chest for marine-based drug discovery targeting neurodegenerative diseases. We overview the natural products of neurological properties already discovered from its waters and survey the existing molecular and cellular targets for pharmacological modulation of the disease. We further provide a general assessment of the drug discovery potential of the Russian Pacific in case of its systematic development to tackle neurodegenerative diseases.</p

Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models

Mitochondrial dysfunction contributes to numerous chronic diseases, and mitochondria are targets for various toxins and xenobiotics. Therefore, the development of drugs or therapeutic strategies targeting mitochondria is an important task in modern medicine. It is well known that the primary, although not the sole, function of mitochondria is ATP generation, which is achieved by coupled respiration. However, a high membrane potential can lead to uncontrolled reactive oxygen species (ROS) production and associated dysfunction. For over 50 years, scientists have been studying various synthetic uncouplers, and for more than 30 years, uncoupling proteins that are responsible for uncoupled respiration in mitochondria. Additionally, the proteins of the mitochondrial alternative respiratory pathway exist in plant mitochondria, allowing noncoupled respiration, in which electron flow is not associated with membrane potential formation. Over the past two decades, advances in genetic engineering have facilitated the creation of various cellular and animal models that simulate the effects of uncoupled and noncoupled respiration in different tissues under various disease conditions. In this review, we summarize and discuss the findings obtained from these transgenic models. We focus on the advantages and limitations of transgenic organisms, the observed physiological and biochemical changes, and the therapeutic potential of uncoupled and noncoupled respiration