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1.
Role of Hydrogen Sulfide and Polysulfides in Neurological Diseases: Focus on Protein S-Persulfidation.
Sun, HJ, Wu, ZY, Nie, XW, Bian, JS
Current neuropharmacology. 2021;(6):868-884
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Abstract
Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins.
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Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.
Koźmiński, P, Halik, PK, Chesori, R, Gniazdowska, E
International journal of molecular sciences. 2020;(10)
Abstract
Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discussed.
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[Ketogenic diet – mechanism of action and perspectives for the use in the therapy: data from clinical studies].
Pondel, N, Liśkiewicz, D, Liśkiewicz, A
Postepy biochemii. 2020;(3):270-286
Abstract
Ketogenic diet is a high fat and very low-carbohydrate nutritional approach that induces increased production of ketone bodies, which serve as an alternative to glucose energetic substrates. Since almost a century ketogenic diet has been used in the therapy of refractory epilepsy, especially in children. Because of the pleiotropic effect of ketogenic diet on physiology, including inflammation, oxidative stress, energy balance and signaling pathways, in recent years scientists have been intensively exploring the use of it in the treatment of other diseases. In the present article current clinical studies regarding the possibility of using the ketogenic diet in the treatment of obesity, diabetes, neurological disorders and cancer has been reviewed alongside with potential mechanisms responsible for the therapeutic effect of ketogenic diet in these diseases. The metabolic processes engaged in nutritional ketosis and practicals aspects of ketogenic dieting have been also discussed.
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The neurological insights of the emerging coronaviruses.
Msigwa, SS, Wang, Y, Li, Y, Cheng, X
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2020;:1-7
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Abstract
Emerging Viral diseases are incredibly infectious and proficient in inducing pandemics. Unlike the previous emerging coronaviruses (ECoVs) which neurological complexities were uncommon, with neurological features exhibition at 14-25 days post-onset, yet with critical outcomes exhibiting >50% mortality in central nervous (CNS) presenting pathologies. The COVID 19 neurological consequences occur more frequently even in mild cases, presenting with CNS involvement in up to 25%, musculoskeletal and peripheral manifestation (PNM). Through preceding ECoVs case reports, the PNM not linked to fatal outcomes, however, required, repeated neuro-imaging as notable CT and MRI changes appeared as late as 21 days while the likelihood of Cerebrospinal fluid to test positive for ECoV was 25%, only in the CNS presenting cases. Owing to 44-60% myalgia presentation, risk of the high inflammatory state, and coagulation cascade abnormalities reported in ECoVs, testing for C-reactive protein, serum creatine kinase, and D-dimer level is mandatory. Presently, there is no antiviral medication or vaccination for the ECoVs, early induction of antiviral drugs remains the backbone of management. Neurologically, the therapeutic dosages of anticoagulants are linked to the high incidence of thrombotic complexities, while methylprednisolone is associated with myopathy. Future studies expected to apply more neuro-imaging techniques for CNS exploration and further explore the pathogenesis of the COVID 19 myalgia, anosmia/ageusia reported in the majority of the initial cases.
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An expanding spectrum of complications in isolated methylmalonic aciduria.
Forny, P, Grunewald, S
Journal of mother and child. 2020;(2):9-13
Abstract
Isolated methylmalonic acidurias represent a heterogeneous genetic group of inborn errors of propionate metabolism with the common biochemical hallmark of elevated methylmalonic acid present in tissues and body fluids. It was first described in the 1960s and over the years better understanding of the disease and its presentation, earlier diagnosis, and most importantly advances in treatment have resulted in extended survival of patients. With that an expanding spectrum of complications is emerging which requires attention and regular monitoring to facilitate early intervention and reduce disease burden.
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Endothelial dysfunction in neuroprogressive disorders-causes and suggested treatments.
Morris, G, Puri, BK, Olive, L, Carvalho, A, Berk, M, Walder, K, Gustad, LT, Maes, M
BMC medicine. 2020;(1):305
Abstract
BACKGROUND Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. MAIN TEXT Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. CONCLUSIONS Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
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Nutraceuticals in Neurological Disorders.
Makkar, R, Behl, T, Bungau, S, Zengin, G, Mehta, V, Kumar, A, Uddin, MS, Ashraf, GM, Abdel-Daim, MM, Arora, S, et al
International journal of molecular sciences. 2020;(12)
Abstract
Neurological diseases are one of the major healthcare issues worldwide. Posed lifestyle changes are associated with drastically increased risk of chronic illness and diseases, posing a substantial healthcare and financial burden to society globally. Researchers aim to provide fine treatment for ailing disorders with minimal exposed side effects. In recent decades, several studies on functional foods have been initiated to obtain foods that have fewer side effects and increased therapeutic activity. Hence, an attempt has been made to unravel several extraction techniques to acquire essential bioactive compounds or phytochemicals from therapeutically active food products. This has led to the conception of the term functional foods being meddled with other similar terms like "pharmafoods," "medifoods", "vitafoods", or "medicinal foods". With a dire need to adhere towards healthy options, the demand of nutraceuticals is widely increasing to combat neurological interventions. An association between food habits and the individual lifestyle with neurodegeneration has been manifested, thereby proposing the role of nutraceuticals as prophylactic treatment for neurological interventions. The current review covers some of the major neurological disorders and nutraceutical therapy in the prevention of disease.
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αB-crystallin as a promising target in pathological conditions - A review.
Maksimiuk, M, Sobiborowicz, A, Tuzimek, A, Deptała, A, Czerw, A, Badowska-Kozakiewicz, AM
Annals of agricultural and environmental medicine : AAEM. 2020;(3):326-334
Abstract
INTRODUCTION AND OBJECTIVE αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.
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Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease.
Estrada, JA, Contreras, I
Nutrients. 2019;(5)
Abstract
The gut-microbiome-brain axis is now recognized as an essential part in the regulation of systemic metabolism and homeostasis. Accumulating evidence has demonstrated that dietary patterns can influence the development of metabolic alterations and inflammation through the effects of nutrients on a multitude of variables, including microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. These signaling molecules are, in turn, implicated in the regulation of the immune system, either promoting or inhibiting the production of pro-inflammatory cytokines and the expansion of specific leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Metabolic diseases, like obesity and type 2 diabetes mellitus, are related to inadequate dietary patterns and promote variations in the aforementioned signaling pathways in patients with these conditions, which have been linked to alterations in neurological functions and mental health. Thus, maintenance of adequate dietary patterns should be an essential component of any strategy aiming to prevent neurological pathologies derived from systemic metabolic alterations. The present review summarizes current knowledge on the role of nutrition in the modulation of the immune system and its impact in the development of neuroinflammation and neurological disease.
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Food and Food Products on the Italian Market for Ketogenic Dietary Treatment of Neurological Diseases.
Leone, A, De Amicis, R, Lessa, C, Tagliabue, A, Trentani, C, Ferraris, C, Battezzati, A, Veggiotti, P, Foppiani, A, Ravella, S, et al
Nutrients. 2019;(5)
Abstract
The ketogenic diet (KD) is the first line intervention for glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency, and is recommended for refractory epilepsy. It is a normo-caloric, high-fat, adequate-protein, and low-carbohydrate diet aimed at switching the brain metabolism from glucose dependence to the utilization of ketone bodies. Several variants of KD are currently available. Depending on the variant, KDs require the almost total exclusion, or a limited consumption of carbohydrates. Thus, there is total avoidance, or a limited consumption of cereal-based foods, and a reduction in fruit and vegetable intake. KDs, especially the more restrictive variants, are characterized by low variability, palatability, and tolerability, as well as by side-effects, like gastrointestinal disorders, nephrolithiasis, growth retardation, hyperlipidemia, and mineral and vitamin deficiency. In recent years, in an effort to improve the quality of life of patients on KDs, food companies have started to develop, and commercialize, several food products specific for such patients. This review summarizes the foods themselves, including sweeteners, and food products currently available for the ketogenic dietary treatment of neurological diseases. It describes the nutritional characteristics and gives indications for the use of the different products, taking into account their metabolic and health effects.