c-Myc and FOXO3a-The Everlasting Decision Between Neural Regeneration and Degeneration.

The transcription factors c-Myc and FoxO3a play significant roles in neurodegenerative processes, yet their interaction in neurological disorders remains largely unexplored. In contrast, much of the available information about their relationship comes from cancer research. While it is well-established that FoxO3a inhibits c-Myc activity, this interaction represents only a basic understanding of a far more complex dynamic, which includes exceptions under specific conditions and the involvement of additional regulatory factors.

An Alternative Photothrombotic Model of Transient Ischemic Attack.

Animal models mimicking human transient ischemic attack (TIA) and cerebral microinfarcts are essential tools for studying their pathogenetic mechanisms and finding methods of their treatment. Despite its advantages, the model of single arteriole photothrombosis requires complex experimental equipment and highly invasive surgery, which may affect the results of further studies. Hence, to achieve high translational potential, we focused on developing a TIA model based on photothrombosis of arterioles to combine good reproducibility and low invasiveness.

Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson's Disease.

Heat shock protein 70 (HSP70) is activated under stress response. Its involvement in cell protection, including energy metabolism and quality control makes it a promising pharmacological target. A strategy to increase HSP70 levels inside the cells is the application of recombinant HSP70.

Exogenous Hsp70 exerts neuroprotective effects in peripheral nerve rupture model.

Hsp70 is the main molecular chaperone responsible for cellular proteostasis under normal conditions and for restoring the conformation or utilization of proteins damaged by stress. Increased expression of endogenous Hsp70 or administration of exogenous Hsp70 is known to exert neuroprotective effects in models of many neurodegenerative diseases. In this study, we have investigated the effect of exogenous Hsp70 on recovery from peripheral nerve injury in a model of sciatic nerve transection in rats.

Modeling transient ischemic attack via photothrombosis.

The health significance of transient ischemic attacks (TIAs) is largely underestimated. Often, TIAs are not given significant importance, and in vain, because TIAs are a predictor of the development of serious cardiovascular diseases and even death. Because of this, and because of the difficulty in diagnosing the disease, TIAs and related microinfarcts are poorly investigated.

Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke.

p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53.

The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.

Ischemic stroke is a leading cause of disability and mortality worldwide. The only approved treatment for ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA), though this approach often leads to a severe complication: hemorrhagic transformation (HT). The pathophysiology of HT in response to tPA is complex and not fully understood.

Expression of Amyloid Precursor Protein, Caveolin-1, Alpha-, Beta-, and Gamma-Secretases in Penumbra Cells after Photothrombotic Stroke and Evaluation of Neuroprotective Effect of Secretase and Caveolin-1 Inhibitors.

Our studies reveal changes in the expression of the main participants in the processing of amyloid precursor protein (APP) in neurons and astrocytes after photothrombotic stroke (PTS). Here we show the increase in the level of N- and C-terminal fragments of APP in the cytoplasm of ischemic penumbra cells at 24 h after PTS and their co-immunoprecipitation with caveolin-1. The ADAM10 α-secretase level decreased in the rat brain cortex on the first day after PTS.

Histone Deacetylases as Epigenetic Targets for Treating Parkinson's Disease.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of PD patients but cannot completely cure the disease. Therefore, exploring other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable.

Sirtuins 1 and 2 in the Acute Period After Photothrombotic Stroke: Expression, Localization and Involvement in Apoptosis.

Sirtuins (SIRTs) are NAD- dependent histone deacetylases. They are involved in a variety of biological pathways and are thought to be a promising target for treating several human disorders. Although evidence is piling up to support the neuroprotective role of SIRTs in ischemic stroke, the role of different sirtuin isoforms needs further investigation.

E2F1 Expression and Apoptosis Initiation in Crayfish and Rat Peripheral Neurons and Glial Cells after Axonal Injury.

Neurotrauma is among the main causes of human disability and mortality. The transcription factor E2F1 is one of the key proteins that determine the fate of cells. The involvement of E2F1 in the regulation of survival and death of peripheral nerve cells after axotomy has not been previously studied.

The Role of p53 Protein in the Realization of the Exogenous Heat Shock Protein 70 Anti-Apoptotic Effect during Axotomy.

The search for effective neuroprotective agents for the treatment of neurotrauma has always been of great interest to researchers around the world. Extracellular heat shock protein 70 (eHsp70) is considered a promising agent to study, as it has been demonstrated to exert a significant neuroprotective activity against various neurodegenerative diseases. We showed that eHsp70 can penetrate neurons and glial cells when added to the incubation medium, and can accumulate in the nuclei of neurons and satellite glial cells after axotomy.

Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke.

Background: Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation, histone methylation, etc. Changes in DNA methylation after ischemia can have both neuroprotective and neurotoxic effects depending on the degree of ischemia damage, the time elapsed after injury, and the site of methylation.

Histone Deacetylases and Their Isoform-Specific Inhibitors in Ischemic Stroke.

Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to be effective in protecting the brain from ischemic damage.

The Role of Post-Translational Acetylation and Deacetylation of Signaling Proteins and Transcription Factors after Cerebral Ischemia: Facts and Hypotheses.

Histone deacetylase (HDAC) and histone acetyltransferase (HAT) regulate transcription and the most important functions of cells by acetylating/deacetylating histones and non-histone proteins. These proteins are involved in cell survival and death, replication, DNA repair, the cell cycle, and cell responses to stress and aging. HDAC/HAT balance in cells affects gene expression and cell signaling.

LIM kinase inhibitor T56-LIMKi protects mouse brain from photothrombotic stroke.

: In an ischemic stroke, the damage spreads from the infarction core to surrounding tissues. The present work was aimed at the search of effective neuroprotectors that restrict injury propagation. : We studied possible protective effects of inhibitors of protein kinases LIMK2 (T56-LIMKi), DYRK1A (harmine), and tryptophan hydroxylase (4-chlorophenylalanine) on infarction size and morphology of peri-infarct area after photothrombotic stroke (a model of ischemic stroke) in mouse brain.

Localization and Expression of Sirtuins 1, 2, 6 and Plasticity-Related Proteins in the Recovery Period after a Photothrombotic Stroke in Mice.

Sirtuins, class III histone deacetylases, are involved in the regulation of tissue repair processes and brain functions after a stroke. The ability of some isoforms of sirtuins to circulate between the nucleus and cytoplasm may have various pathophysiological effects on the cells. In present work, we focused on the role of non-mitochondrial sirtuins SIRT1, SIRT2, and SIRT6 in the restoration of brain cells following ischemic stroke.

Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke.

Ischaemic stroke is an acute interruption of the blood supply to the brain, which leads to rapid irreversible damage to nerve tissue. Ischaemic stroke is accompanied by the development of neuroinflammation and neurodegeneration observed around the affected brain area. Heat shock protein 70 (Hsp70) facilitates cell survival under a variety of different stress conditions.

Overexpression of HDAC6, but not HDAC3 and HDAC4 in the penumbra after photothrombotic stroke in the rat cerebral cortex and the neuroprotective effects of α-phenyl tropolone, HPOB, and sodium valproate.

Epigenetic processes play important roles in brain responses to ischemic injury. We studied effects of photothrombotic stroke (PTS, a model of ischemic stroke) on the intracellular level and cellular localization of histone deacetylases HDAC3, HDAC4 and HDAC6 in the rat brain cortex, and tested the potential neuroprotector ability of their inhibitors. The background level of HDAC3, HDAC4 and HDAC6 in the rat cerebral cortex was relatively low.

The Expression and Localization of Histone Acetyltransferases HAT1 and PCAF in Neurons and Astrocytes of the Photothrombotic Stroke-Induced Penumbra in the Rat Brain Cortex.

Stroke is one of the leading reasons of human death. Ischemic penumbra that surrounds the stroke-induced infarction core is potentially salvageable, but molecular mechanisms of its formation are poorly known. Histone acetylation induces chromatin decondensation and stimulates gene expression.

[Objective assessment of mental nerve local anesthesia].

Aim: To study the reaction of the mental nerve to selective stimulation of thin nerve fibers by thermal stimuli during conduction anesthesia.

Material And Method: The pilot study involved 24 healthy volunteers: 13 subjects were injected with a 4% solution of articaine-containing anesthetic with a vasoconstrictor in a ratio of 1:200 000 (pH 4.8-5.