Potential Neuroprotectors Research Articles

Neuroprotective Effect of Artemisinin in an Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease in older people, characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of aggregated of hyperphosphorylated tau protein, which normally helps stabilize microtubules in neurons. Nowadays, artemisinin (ART) as well as its semisynthetic derivatives (ARTs) are seen as potential neuroprotectors. The goal of the present study is the assessment of neuroprotective, antibacterial activity of ART, as well as in silico studies of ART affinity to Aβ-peptides and the search of potential targets for ART. The study is referring to explores the impact of ART on an animal model of AD that is induced by the aggregated amyloidogenic peptide Aβ1-42 by electrophysiology and morphology analysis. Specifically, the focus is on the activation of the entorhinal cortex (ENT) as synaptic potentiation. Electrophysiological and histochemical have demonstrated that therapeutic injection of ART or its derivatives acts as a neuroprotective This treatment appears to prevent or slow down damage to brain tissue, and it promotes the restoration of neurons and their surrounding environment. The protective effects of ART may involve various mechanisms, including antioxidant activity, anti-inflammatory effects, and the inhibition of apoptosis. in silico studies revealed a direct, strong interaction of ART with the amyloidogenic peptides 5Aβ17-42, 12Aβ9-40, and 18Aβ9-40. in silico screening revealed several protein targets for ART, including cytochrome P-450 2B6 (CYP2B6). The highest binding affinity was found on the active site of CYP2B6. ART has great potential for discovering new drugs using combined therapies.

Антиоксидантные эффекты синтетического аналога тиронамина при экспериментальной ишемии головного мозга

The oxidative stress associated with ischemic stroke is a major factor damaging the nervous tissue. Thyroid hormones have a significant effect on the body’s redox status, however, the impact of their derivatives, thyronamines, considered as potential neuroprotectors, on the characteristics of lipid peroxidation (LP) is not clearly understood. The study was aimed to assess the impact of the Т0АМ thyronamine synthetic analogue on the main LP indicators in the model of acute cerebral ischemia. Permanent ligation of the right common carotid artery was performed to simulate acute cerebral ischemia in white rats. The animals were divided into two groups: the control group receiving no treatment and the experimental group, to which the Т0АМ thyronamine synthetic analogue was intraperitoneally administrated (75 mg/kg of the rat’s body weight). After 24 h the rat was decapitated, and the cerebral cortex tissue was extracted for biochemical analysis. The following LP indicators were determined by spectrophotometry: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx). When administering the Т0АМ thyronamine synthetic analogue, a significant (2-fold) decrease in MDA levels was observed in the ischemic hemisphere (р = 0.022), along with the 2.49-fold increase in the GPx activity in the brain tissue (р = 0.004) of the intact hemisphere and the 2.65-fold increase in its activity (р = 0.021) in the ischemic hemisphere, as well as the 1.23-fold increase in SOD activity in the ischemic hemisphere (р = 0.042). The Т0АМ thyronamine synthetic analogue has a great potential in terms of activation of the antioxidant protection mechanisms in the cerebral cortex of white laboratory rats under conditions of acute hemispheric ischemia.

Биофункциональная активность in vivo хлорогеновой кислоты и биоханина А, выделенных из экстрактов каллусной культуры Trifolium pratense L.

Polyphenols are potential neuroprotectors that increase lifespan and slow down aging. Red clover (Trifolium pratense L.) is a promising source of biologically active substances. Its extracts contain biochanin A and chlorogenic acid. This research used Caenorhabditis elegans to study the effect of polyphenols extracted from red clover callus cultures on SOD-3 and HSP-16.2 genes, as well as their anti-amyloid potential. 
 The chlorogenic acid and biochanin A (200, 100, 50, and 10 µM) with a purity of 95% were isolated from callus extracts of T. pratense L. The effect of polyphenols on SOD-3 and HSP-16.2 was assessed after 5 and 2 h of heat stress (35°C), respectively, using C. elegans N2 Bristol as model organism. The neuroprotective potential was measured by counting paralyzed nematodes after 18, 40, and 62 h of incubation.
 The research established a dose-dependent effect between the concentration of biologically active substances and the percentage of paralyzed nematodes after 18 h of cultivation. The lowest paralysis phenotype count occurred at a concentration of 200 μM. The activity of 200 μM biochnin A was 1.18 times as high as that of a 200 μM chlorogenic acid solution. Biochanin A solutions increased SOD-3 expression by 3.7 times, compared to the control.
 The biologically active substances exhibited relative neuroprotective activity and affected the expression of antioxidant defense gene in C. elegans.

Constituent isoflavones of Puerariae radix as a potential neuroprotector in cognitive impairment: Evidence from preclinical studies.

With the increasing aging population worldwide, the incidence of senile cognitive impairment (CI) is increasing, posing a serious threat to the health of elderly persons. Despite developing new drugs aimed at improving CI, progress in this regard has been insufficient. Natural preparations derived from plants have become an unparalleled resource for developing new drugs. Puerariae radix (PR) has a long history as Chinese herbal medicine. PR is rich in various chemical components such as isoflavones, triterpenes, and saponins. The isoflavones (puerarin, daidzein, formononetin, and genistein) exhibit potential therapeutic effects on CI through multiple mechanisms. Relevant literature was organized from major scientific databases such as PubMed, Elsevier, SpringerLink, ScienceDirect, and Web of Science. Using "Puerariae radix," "Pueraria lobata," "isoflavones," "puerarin," "antioxidant," "daidzein," "formononetin," "genistein," "Alzheimer"s disease," and "vascular cognitive impairment" as keywords, the relevant literature was extracted from the databases mentioned above. We found that isoflavones from PR have neuroprotective effects on multiple models of CI via multiple targets and mechanisms. These isoflavones prevent Aβ aggregation, inhibit tau hyperphosphorylation, increase cholinergic neurotransmitter levels, reduce neuroinflammation and oxidative stress, improve synaptic plasticity, promote nerve regeneration, and prevent apoptosis. PR has been used as traditional Chinese herbal medicine for a long time, and its constituent isoflavones exert significant therapeutic effects on CI through various neuroprotective mechanisms. This review will contribute to the future development of isoflavones present in PR as novel drug candidates for the clinical treatment of CI.

Enhancing the neuroprotective effect of squid outer skin astaxanthin against rotenone-induced neurotoxicity in in-vitro model for Parkinson's disease.

Rotenone is a widely used organic pesticide that induces neurotoxicity via inhibition of mitochondrial complex I and oxidative stress actions for the most of dopaminergic neurons as that occurring in Parkinsonism disease (PD). Astaxanthin (ASX) is a natural pigment (carotenoids) and a potent therapeutic compound due to its antioxidant and anti-inflammatory properties. The commercially important cephalopod Doryteuthis singhalensis is widely distributed in tropical and subtropical waters in World Ocean. D. singhalensis is an important source of astaxanthin that contains valuable biological active compounds with many valuable pharmacological effects. The present study evaluated the effect of astaxanthin in preventing rotenone-induced toxicity of SK-N-SH human neuroblastoma cells in an in vitro model of experimental Parkinsonism. The results revealed the strongly significant antioxidant capability of extracted squid astaxanthin in 1,1- diphenyl- 2- picrylhydrazyl (DPPH) radical scavenging activity. In addition, astaxanthin treatment based on dose dependent manner significantly attenuated rotenone induced cytotoxicity, mitochondrial dysfunction and oxidative stress in SKN- SH cells. It is concluded that the marine squid derived astaxanthin could be used as a potential neuroprotector against rotenone induced toxicity due to its antioxidant, and anti-apoptotic properties. Consequently, it could be a supportive remedy for neurodegenerative diseases like Parkinson's disease.

Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries.

Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein-protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood-brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke.

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers.

Ex vivo model of spontaneous neuroretinal degeneration for evaluating neuroprotection

AbstractEx vivo neuroretina models are considered adequate tools for improving the knowledge of retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, immunohistochemistry, electrophysiology and molecular biology techniques can be applied over retinal explant cultures.Although several cell culture‐based techniques have been developed to investigate retinal function, such as retinal cells primary cultures, co‐cultures with retinal pigment epithelium (RPE) cells, or 3D aggregates cultures, ex vivo models provide a better alternative to animal experimentation and are inexpensive and easy to develop. Limitations of these ex vivo systems include the absence of choroidal and retinal blood flow, the lack of vitreous and RPE, and the axotomy of the ganglion cells, which considerably limit the evaluation of the inner retina modifications. However, these limitations are also critical for the retina to degenerate spontaneously and progressively as the culture progresses.Neuroretina culture systems began to develop in the 1920 s, using chicken embryos' retinas and posteriorly mammalian retinas. In 1954, Trowell developed the membrane culture method, in which the retina was placed with the vitreous surface in contact with a supporting porous membrane and maintained at an air‐medium interface. In 1989, Caffé et al. cultured the neuroretina with the photoreceptors layer facing downward over porous membrane, the technique that is currently considered the gold standard. Since then, ex vivo mammal neuroretina cultures from rats, mice, hamsters, guinea pigs, rabbits, cats, dogs, pigs, cows or primate, have been used to describe the differentiation processes of post‐natal retinas; to provide valuable insights into retinal diseases processes; to test potential therapeutic substances; to examine the role of growth factors over retinal cells' dynamics; to assess nanostructured scaffolds and their potential cytotoxicity, and to evaluate potential advanced therapies.Although mammal neuroretina is an excellent alternative to the dependency on post‐mortem human eyes, ex vivo human neuroretina cultures have also been characterized. They have improved the current knowledge about photoreceptors, ganglion cells, glial cells and microglia dynamics. Furthermore, human tissues are theoretically better suited for translational research than animal cells and perhaps even animal models, which exponentially increases the usefulness of the neuroretina cultures, and the extrapolation of the results obtained, marking a promising future for the screening and evaluation of potential neuroprotectors.

Kaempferol as a potential neuroprotector in Alzheimer's disease.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is largely associated with cognitive disability, amnesia, and abnormal behavior, which accounts for about two third of people with dementia worldwide. A growing body of research demonstrates that AD is connected to several factors, such as aberrant accumulation of amyloid-beta (Aβ), increase in the hyperphosphorylation of Tau protein, and the formation of neurofibrillary tangles, mitochondrial dysfunction, and inordinate production of reactive oxygen species (ROS). Despite remarkable efforts to realize the etiology and pathophysiology of AD, until now, scientists have not developed and introduced medications that can permanently cease the progression of AD. Thus, nowadays, research on the role of natural products in the treatment and prevention of AD has attracted great attention. Kaempferol (KMP), one of the prominent members of flavonols, exerts its ameliorative actions via attenuating oxidative stress and inflammation, reducing Aβ-induced neurotoxicity, and regulating the cholinergic system. Therefore, in this review article, we outlined the possible effects of KMP in the prevention and treatment of AD. PRACTICAL APPLICATIONS: Kaempferol (KMP) exerts its ameliorative actions against AD via attenuating oxidative stress and inflammation, reducing Aβ-induced neurotoxicity, and regulating the cholinergic system. The beneficial effects of KMP were addressed in both in vitro and in vivo studies; however, conducting further research can warrant its long-term effects as a safe agent. Therefore, after confirming its favorable functions in the prevention and treatment of AD, it could be used as a safe and effective agent.

Subjective memory complaints as a predictor of mild cognitive impairment and Alzheimer\u2019s disease

While there is a multitude of studies on mild cognitive impairment (MCI; more than 80,000 articles), subjective memory complaints (SMC) have received less attention as a prodromal stage of Alzheimer’s disease (AD; less than 2000 articles). In this perspective review article, we argue that SMC should also be considered as another risk factor for the development of AD, and perhaps a pre-MCI condition. This recognition of SMC could help clinicians to identify individuals at risk of developing dementia and could provide protective treatment for them. Accordingly, in this perspective article, we review key studies that outline the nature of SMC, discuss how SMC is measured, explore SMC in MCI, introduce some approaches to SMC treatment, and we discuss future directions for SMC research. Overall, we argue that, like MCI, there should be more research on SMC as a risk factor for developing AD. Consequentially, we aim to highlight the need for further research on SMC and the condition’s role as a potential neuroprotector against AD (e.g., early-stage marker).

FK506 Treatment Prevents Retinal Nerve Fiber Layer Thinning in Organ-Transplanted Glaucoma Patients: A Retrospective Longitudinal Study.

PurposeThis is a retrospective study of primary open-angle glaucoma patients treated with the immunosuppressor FK506 (tacrolimus) after an organ transplant. We assessed whether FK506 might be a potential neuroprotector adjuvant in glaucoma therapy.Patients and methodsOrgan transplant patients treated with FK506 for one or more years between 2006 and 2017 at the University of Texas Medical Branch (UTMB) were enrolled. Those selected were patients older than or equal to 50 years of age and had an ophthalmological eye examination with or without diagnostic tests for primary open-angle glaucoma (POAG). Sixty-one eligible subjects were included in the study and matched with the non-FK506 control group for age, gender, race, and follow-up visits.ResultsA lower incidence of POAG was noted in the FK506-treated patients (15%) when compared to the non-FK506 group (22%), though not significant (p=0.34). Among POAG subjects, the average retinal nerve fiber layer (RNFL) thickness decreased at a rate of 1.4 µm per year (p=0.0001) in the non-FK506 control patients versus 0.4 µm per year (p=0.34) in the FK506 patients. The superior and inferior RNFL quadrants in the control non-FK506 group had a thinning of 2.2 µm and 2.3 µm per year, respectively, (p=0.003 and p=0.0001), while in the FK506 patients, there was no significant loss. In addition, RNFL thinning in nasal and temporal quadrant also showed less reduction in FK506-treated subjects but was not statistically significant (p=0.68 and p=0.93).ConclusionFK506 therapy offers a new promising avenue for neuroprotection in POAG patients and needs to be investigated further for use in conjunction with conventional glaucoma treatments.

POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

Modulation of HSP70-dependent mechanisms of endogenous neuroprotection with selenium derivatives under conditions of ischemic-type acute cerebrovascular accident modeling

The influence of selenium derivatives selenoline, cysteine selenate, and methionine selenate on the main indicators of HSP70-dependent mechanisms of endogenous neuroprotection under conditions of acute cerebrovascular accident (CVA) modeling has been investigated, and pathogenetic substantiation of prospects for their further study as potential neuroprotectors has been given. The experiments have been performed on white Wistar rats by bilateral irreversible ligation of the common carotid artery. Cysteine selenite and methionine selenite at a dose of 30 μg/kg, and selenoline at a dose of 50 μg/kg were introduced intraperitoneally to the experimental animals once-daily for 4 days. Every day for 4 days, the severity of neurological reactions was assessed in points on a stroke-index scale, and the mortality rate in animals was recorded. In the process of biochemical studies of brain tissue, the state of mRNA expression, HSP70 level, hypoxia-induced factors (HIF) – HIF1α and HIF-3α were evaluated using the method of polymerase chain reaction (PCR) with real-time reverse transcription. While false-operated animals developed mild neurological disorders, the control group developed bilateral ptosis, circling movements, paresis and paralysis of the limbs. On the 4th day the mean score on Stroke-index P. McGraw neurological deficit assessment scale was 16.7 ± 0.52, and 40 % of animals survived. In the cytosol and mitochondria of brain tissues, a decrease in HSP70 was detected by 47% and 59%, respectively. The administration of selenite cysteine, selenite methionine and selenoline contributed to the normalization of this indicator, to a greater extent under the action of selenite cysteine. In the control group there was a decrease in HSP70 mRNA expression. After administration of all the studied compounds, a tendency to increase the expression of HSP70 mRNA was observed compared to the controls. Under conditions of cerebral circulation insufficiency ACCI, in brain tissue, a decrease in the synthesis of HIF-1α at the stage of translation with ATP deficiency was noted. The course administration of selenium-containing drugs to rats with ACCI induced an increase in HIF1α levels: cysteine selenite – by 11.2 times, selenite methionine – by 3.13 times, and selenoline – by 1.1 times (p ˃0.05). A significant difference in relation to the expression of HIF-3α was shown only after administration of cysteine selenite (by 4.3 times higher than the control). The study of antioxidant modulation of HSP70-dependent mechanisms of endogenous neuroprotection of the brain have demonstrated that administration of selenium-containing medications cysteine selenite, methionine selenite, and selenoline lead to a decrease in neurological signs and the mortality rate in animals with ACCI. The action of selenium-containing drugs is realized due to their positive influence on the glutathione system, the preservation of energy-producing function of organs and mitoprotective effect. The obtained results indicate the relevance of further study of selenium-containing drugs on other models of pathological processes accompanied by ischemia.

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. HDAC3 localized in the nuclei of some neurons and few astrocytes. HDAC4 was found in the neuronal cytoplasm. After PTS, their levels in penumbra did not change, but HDAC4 appeared in the nuclei of some cells. Its level in the cytoplasmic, but not nuclear fraction of penumbra decreased at 24, but not 4 h after PTS. HDAC6 was upregulated in neurons and astrocytes in the PTS-induced penumbra, especially in the nuclear fraction. Unlike HDAC3 and HDAC4, HDAC6 co-localized with TUNEL-positive apoptotic cells. Inhibitory analysis confirmed the involvement of HDAC6, but not HDAC3 and HDAC4 in neurodegeneration. HDAC6 inhibitor HPOB, HDAC2/8 inhibitor α-phenyl tropolone, and non-specific histone deacetylase inhibitor sodium valproate, but not HDAC3 inhibitor BRD3308, or HDAC4 inhibitor LMK235, decreased PTS-induced infarction volume in the mouse brain, reduced apoptosis, and recovered the motor behavior. HPOB also restored PTS-impaired acetylation of α-tubulin. α-phenyl tropolone restored acetylation of histone H4 in penumbra cells. These results suggest that histone deacetylases HDAC6 and HDAC2 are the possible molecular targets for anti-ischemic therapy, and their inhibitors α-phenyl tropolone, HBOP and sodium valproate can be considered as promising neuroprotectors.

Drosophila melanogaster as a Model System for the Study of Human Neuropathy and the Testing of Neuroprotectors

Currently, the molecular characteristics of the occurrence and course of neurodegenerative diseases, which are among the most serious and still incurable illnesses, remain to be fully elucidated. Therefore, the search for novel medicines for the removal, relief, or postponement of symptoms in these pathologies remains relevant. In view of the complexity of undertaking this research in human, the identification of genes associated with developing neurodegenerative changes and the study of their functions in different (neuronal and glial) tissues and at different stages of ontogenesis are carried out in model systems. Drosophila melanogaster is one of the best and available objects for the identification of molecular genetic mechanisms underlying the development of neurodegeneration as well as for the initial tests of novel compounds with neuroprotective properties. This article discusses the methods of genetic analysis in Drosophila, the use of D. melanogaster as a model of human neurodegenerative disorders, and a possibility of using its model as test systems for the study of potential neuroprotectors.

Thymoquinone as a Potential Neuroprotector in Acute and Chronic Forms of Cerebral Pathology.

Thymoquinone is one of the main active components of the essential oil from black cumin (Nigella sativa) seeds. Thymoquinone exhibits a wide range of pharmacological activities, including neuroprotective action demonstrated in the models of brain ischemia/reperfusion, Alzheimer's and Parkinson's diseases, and traumatic brain injury. The neuroprotective effect of thymoquinone is mediated via inhibition of lipid peroxidation, downregulation of proinflammatory cytokines, maintenance of mitochondrial membrane potential, and prevention of apoptosis through inhibition of caspases-3, -8, and -9. Thymoquinone-based mitochondria-targeted antioxidants are accumulated in the mitochondria and exhibit neuroprotective properties in nanomolar concentrations. Thymoquinone reduces the negative effects of acute and chronic forms of brain pathologies. The mechanisms of the pharmacological action of thymoquinone and its chemical derivatives require more comprehensive studying. In this paper, we formulated the prospects of application of thymoquinone and thymoquinone-based drugs in the therapy of neurodegenerative diseases.

The Effect of Sulfur-Containing Compounds on the Quinoid Process of Adrenaline Autoxidation; Potential Neuroprotectors

The Effect of Sulfur-Containing Compounds on the Quinoid Process of Adrenaline Autoxidation; Potential Neuroprotectors

Epigenetic Mechanisms of Ischemic Stroke

Stroke is one of the main causes of human death and disability. Occlusion of the cerebral vessels in minutes leads to oxygen and glucose depletion and the infarction of nervous tissue. However, neuroprotectors that can rescue neurons have not been found yet. This review describes the biochemical processes leading to cell death in the ischemic brain and the molecular factors that spread the damage to neighboring tissues and form the transition zone (penumbra). Even though ischemic damage generally suppresses biosynthetic processes, some proteins are expressed in the ischemic penumbra. Epigenetic processes are the mechanisms of the global regulation of transcription and protein synthesis as well as the functional state of cells. The review considers main epigenetic processes that regulate gene expression and protein synthesis: DNA methylation, methylation and acetylation of histones. The main attention is paid to epigenetic regulatory proteins: DNA methyltransferases, histone acetyltransferases, histone deacetylases and their isoforms. Their role in the brain responses to ischemic damage is discussed. The inhibition of some epigenetic proteins is one of the promising strategies for the treatment of ischemic stroke. The capabilities of some inhibitors of histone deacetylases and DNA methyltransferases as potential neuroprotectors in ischemic stroke are discussed.

Expression of Vascular Endothelial Growth Factor in the Rat Brain after Perinatal Hypoxia and Pharmacological Correction

—We studied the role of vascular endothelial growth factor (VEGF) in post-hypoxic damage of the rat brain and in the effect of saliphene, a GABA derivative that is considered as a potential neuroprotector. The method of quantitative immunohistochemistry was used to evaluate the expression of VEGF in the rat brain (neocortex and hippocampus) at the early and late periods after perinatal hypoxia and the subsequent administration of saliphene. Hypoxia resulted in an increase in the expression of vascular endothelial growth factor in the developing rat brain, and injections of saliphene prevented an increase in VEGF expression, leaving this index at the level of the control values. Thus, the changes the expression of vascular endothelial growth factor (VEGF) in the rat brain after perinatal hypoxia may be considered as a marker of the neuroprotective effect of saliphene.

Isoalantolactone amino derivatives as potential neuroprotectors

Isoalantolactone amino derivatives as potential neuroprotectors