Neurochemical Journal最新文献

Abstract

Alzheimer’s disease is an age-associated progressive disorder, characterized by neurodegeneration and following cognitive decline. Several pathological alterations are implicated in its pathogenesis, hence etiology is still poorly understood. Ferroptosis is an alternative form of cell death, driven by intracellular accumulation of iron with subsequent reactive oxygen species formation, which damages membranes, proteins, and DNA, causing cell death. The imbalance in iron homeostasis is rapidly gaining weight as a neurodegeneration cause, increasing the need to develop in vivo and in vitro models to understand the role of ferroptosis in Alzheimer’s disease pathogenesis. This review focuses on the mechanisms of ferroptosis in the pathogenesis of AD, giving a detailed overview of the available in vivo and in vitro methods and their applications, as well as describing in detail the ferrous amyloid buthionine (FAB) model.

Abstract—Disruption of neuroimmune regulatory relationships caused by a change in the functional phenotype of immune cells due to chronic ethanol intoxication is an essential link in the pathogenesis of alcoholism. The unidirectional influence of most psychoactive drugs on the cells of the nervous and immune systems allows one to consider immune cells as model objects for influencing intersystem functional relationships. Based upon our own priority data on the presence of immunomodulatory properties of the original anticonvulsant acting on the molecular targets of ethanol in the central nervous system and the immune system in chronic alcohol intoxication, the aim of the present study was to evaluate the central effects of peripherally injected lymphocytes with the in vitro modulated functional activity by a synthetic ligand of the GABAA-receptor complex meta-chlorobenzhydrylurea in long-term alcoholized animals. It was shown that transplantation of lymphocytes precultured with the anticonvulsant in syngeneic long-term alcoholic recipients achieves a decrease in alcohol motivation and stimulation of behavioral activity in the “open field” test. Editing of behavioral patterns characteristic of chronic alcohol intoxication was recorded against the background of a decrease in proinflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ and an increase in the anti-inflammatory cytokine IL-10 in pathogenetically significant brain structures, as well as an increase in the level of BDNF in the hippocampus, which allows us to consider a decrease in neuroinflammation and stimulation neuroplasticity as possible mechanisms for modification of the behavior of recipients. Visualization of functionally active lymphocytes precultured with meta-chlorobenzhydrylurea in the brain parenchyma of long-term alcoholized recipients also suggests a direct effect of injected lymphocytes on CNS cells. Thus, immune cells modulated in vitro with meta-chlorobenzhydrylurea by relatively independent mechanisms have positive psychoneuromodulating effects in chronic ethanol intoxication, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.

Abstract

Parkinson’s disease (PD), a neurodegenerative movement disorder, is clinically manifested by disturbances in motor functions and non-motor symptoms, caused by progressive degeneration of nigrostriatal dopaminergic neurons and neurons in selected areas of the central and peripheral nervous system. The multifaceted pathogenesis of PD is associated with sustained mitochondrial dysfunction, oxidative stress, aberrant Са²⁺ homeostasis, which contribute to the activation of Са²⁺-dependent protease calpain. Calpain plays role in neuronal signaling mechanisms, ensuring the normal course of intracellular neurochemical and neurophysiological processes. In neuropathological conditions, elevation of intracellular Ca²⁺ and calpain activation, downregulation of endogenous and/or absence of exogenous pharmacological inhibitors of calpain, instigate calpain-mediated activation of apoptotic pathways, leading to degeneration and loss of selectively vulnerable nigrostriatal dopaminergic neurons in the brain. We have shown that at experimental (in vivo, in vitro) and human (postmortem) PD dorsal neurons and ventral motoneurons of the spinal cord are also affected through the calpain-mediated mechanisms of neurodegeneration. Synthetic calpain inhibitors – calpeptin, SNJ1945, and SJA6017, exhibited neuroprotective effects in the brain and spinal cord (in vivo, in vitro), suggesting calpain as a prospective target molecule for pharmacological therapy in the brain and spinal cord at PD.

Abstract— Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. The pathophysiological mechanisms leading to the development of DPN have not been fully studied and are still debatable. Currently, immune-mediated mechanisms of its development are being discussed. The aim of this study was to estimate the content of TNF-α in the blood serum of patients with diabetes mellitus type 2 (DM2) complicated by DPN and to assess the significance of this factor in the development and progression of DPN. An open comparative study was conducted with the participation of 83 patients with DM2 of different duration. In patients with clinical manifestations of DPN and long-term course of DM2 (group 2), the level of TNF-α was significantly higher compared to patients with DM2 and duration of DPN less than 2 years. Both studied groups of patients with DM2 and DPN had a higher level of TNF-α in comparison with the control group. Our data indicate a more aggressive immune-mediated process that develops with a longer duration of DM2 and makes a negative contribution to the functioning of the peripheral nerve fiber.

Abstract—Extracellular vesicles are macromolecular complexes produced by virtually all types of eukaryotic and prokaryotic cells. According to modern concepts, they allow cells to exchange information, regulate each other’s activity and coordinate their actions during the complex processes of development, maintaining homeostasis, tissue regeneration, etc. Extracellular vesicles have a number of unique properties: the ability to accumulate certain types of proteins and nucleic acids, protect them from degradation and ensure their delivery to target cells, which can be used to create biomimetic approaches to the therapy of a wide range of diseases. The composition of vesicles, the preference for docking with a particular cell type, and ultimately their therapeutic potential are very flexible parameters and are highly dependent on the type and properties of the producer cell culture, as well as cultivation conditions. This review gives an idea of the state and prospects of the therapeutic strategies based on the application of extracellular vesicles for neuroprotection and stimulation of brain tissue regeneration after injury, and also considers existing clinical studies which use extracellular vesicles in the field of neurology and neurosurgery. Particular attention in the review is given to new promising approaches to increasing the production of extracellular vesicles, manipulating their contents, and increasing the efficiency of targeted docking in order to increase their therapeutic activity and specificity.

Abstract

The search for biological markers of neurodegenerative diseases, namely, Alzheimer’s (AD) and Parkinson’s (PD) diseases, is actual problem for fundamental biology and modern medicine. The aim of this review was to present some new results on biomarkers of these neurodegenerative disorders, mainly in biological fluids, like plasma and cerebrospinal fluid. Novel biomarkers in AD include plasma assays for amyloid-β and phosphorylated tau and PET (positron emission tomography) scans, which show great promise for clinical and research use. In PD research, serum cystatin C (Cst3) and homocystein in PD patients were higher than in serum of the normal control group and they were considered as new inflammatory biomarkers. Cst3 in biological fluids was suggested as a promising biomarker for diagnosing PD. Recently, extracellular vesicles (exosomes) have been reported as a new concept in the biomarker field. Serving as transfer vehicles between cells, they represent a promising source of biomarkers for a number of diseases, including neurodegenerative disorders. To date, developmental mechanisms and approaches to the treatment of neurodegenerative diseases (AD, PD) seemingly are extremely relevant, requiring common solutions and the development of new approaches.

Abstract

In recent years, neurodegenerative diseases (NDs) have increased around the world and current treatments only provide temporary relief of the symptoms. So, we aimed to investigate the neuroprotective effects and possible mechanisms of bromelain on the main NDs such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple sclerosis (MS). In this systematic review, we followed the PRISMA checklist 2020 guidelines. Embase, PubMed, Web of Science, Scopus, and Cochrane Library were searched for related articles published before August 1, 2023, using the combination of keywords that were derived based on MeSH terms and similar systematic review studies. The required information was extracted from the publications and recorded in Excel form, and the outcome and mechanisms were reviewed. Finally, 17 studies were selected for the investigation. Bromelain alleviates neuroinflammation by downregulating pro-inflammatory cytokines in the central nervous system. Bromelain also neutralizes free radicals and up-regulated levels of endogenous antioxidant enzymes and improves mitochondrial function in neural cells. So, by antioxidant and anti-inflammatory activity, bromelain neutralizes apoptosis and neuronal damage. Moreover, the immune response in the CNS may be regulated by bromelain. apoptosis and neuronal damage. This proteolytic enzyme also reduced β-amyloid aggregation in AD. In vivo, in vitro, and ex vivo studies revealed that bromelain shows promising neuroprotective effects on NDs by reducing inflammatory factors, and oxidative stress, regulating the immune system, and reducing neurotoxicity. However, more clinical trial studies are needed in this field.

Abstract—Recent scientific studies indicate that angiogenesis and neurogenesis are interrelated processes that determine the functional outcome after ischemic stroke. This literature review presents current data on neurovascular interactions in ischemic stroke and describes the role of the family of vascular endothelial growth factors in the regulation of angiogenesis and neurogenesis, which play a leading role in neuronal survival and neuroplasticity. The authors searched the literature on the pathophysiological role of VEGF in acute cerebral ischemia using the relevant keywords on the PubMed and Google Scholar search engines, as well as Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, eLibrary, and other databases. Clinical studies evaluating the role of VEGF in ischemic stroke are in most cases based on animal models, and their results are ambiguous, which is determined by the versatility of its action. VEGF is an important regulator of angiogenesis, neuroprotection, and neurogenesis, but its negative effect has also been proven in the form of an increase in the permeability of the BBB and, consequently, cerebral edema, as well as the activation of inflammatory processes. Thus, further study of VEGF is needed to determine its role in functional recovery after ischemic stroke.

Abstract

Academician H. Buniatian is recognized as a founder of neurochemistry in Armenia. His research was focused, in particular, on the formation of ammonia in the brain, metabolism of copper, the role of GABA in brain function and the whole organism homeostasis. H. Buniatian was among the founders of Armenian Academy of Sciences. He also established the All-Union journal “Neirokhimiya” (at present there is also an English version is Neurochemical Journal). Academician A. Galoyan, the first Editor-in-Chief of this journal, was a renowned modern neuroendocrinologist. He discovered and isolated from different parts of the brain a number of neurohormones and peptides, thus forming the foundation for the concepts of the brain immune system, as well as endocrine heart.

Abstract—The aim of the work was to study the level of nerve growth factor (NGF) in the serum of patients with melancholic depression. The examined group consisted of 23 patients. Upon admission to the clinic, before therapy began, the patients showed a significantly higher (278.28 pg/mL) level of NGF in the serum compared with control (239.51 ± 22.15) (p < 0.05). We believe that the increased level of NGF in serum in patients with melancholic depression may be associated with impaired functioning of the BBB and an increase in its permeability for neurotropic factor.