scholarly journals Gut–Brain Axis and Neurodegeneration: State-of-the-Art of Meta-Omics Sciences for Microbiota Characterization

2020 ◽  
Vol 21 (11) ◽  
pp. 4045 ◽  
Author(s):  
Bruno Tilocca ◽  
Luisa Pieroni ◽  
Alessio Soggiu ◽  
Domenico Britti ◽  
Luigi Bonizzi ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Integrated Approach ◽  
Microbial Genomes ◽  
Physiological Processes ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Recent advances in the field of meta-omics sciences and related bioinformatics tools have allowed a comprehensive investigation of human-associated microbiota and its contribution to achieving and maintaining the homeostatic balance. Bioactive compounds from the microbial community harboring the human gut are involved in a finely tuned network of interconnections with the host, orchestrating a wide variety of physiological processes. These includes the bi-directional crosstalk between the central nervous system, the enteric nervous system, and the gastrointestinal tract (i.e., gut–brain axis). The increasing accumulation of evidence suggest a pivotal role of the composition and activity of the gut microbiota in neurodegeneration. In the present review we aim to provide an overview of the state-of-the-art of meta-omics sciences including metagenomics for the study of microbial genomes and taxa strains, metatranscriptomics for gene expression, metaproteomics and metabolomics to identify and/or quantify microbial proteins and metabolites, respectively. The potential and limitations of each discipline were highlighted, as well as the advantages of an integrated approach (multi-omics) to predict microbial functions and molecular mechanisms related to human diseases. Particular emphasis is given to the latest results obtained with these approaches in an attempt to elucidate the link between the gut microbiota and the most common neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

scholarly journals The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches

2021 ◽  
Vol 22 (9) ◽  
pp. 4630
Author(s):  
Agnieszka Kulczyńska-Przybik ◽  
Piotr Mroczko ◽  
Maciej Dulewicz ◽  
Barbara Mroczko
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Pleiotropic Functions ◽  
Lateral Sclerosis

Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

scholarly journals The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 121 ◽  
Author(s):  
Yonghee Kim ◽  
Jinhong Park ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Bk Channel ◽  
Cns Injury ◽  
Antioxidant Agents ◽  
The Central Nervous System

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

Regulatory role of NGFs in neurocognitive functions

2017 ◽  
Vol 28 (6) ◽  
pp. 649-673 ◽  
Author(s):  
Ashutosh Kumar ◽  
Vikas Pareek ◽  
Muneeb A. Faiq ◽  
Pavan Kumar ◽  
Khursheed Raza ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Current Evidence ◽  
Future Research ◽  
Neurocognitive Dysfunction ◽  
Neurocognitive Functions ◽  
The Central Nervous System ◽  
Health And Disease

AbstractNerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain. They have also been associated extensively with brain disorders characterized by neurocognitive dysfunction. In the present article, we aimed to make an exhaustive review of literature to get a comprehensive view on the role of NGFs in neurocognitive functions in health and disease. Starting with historical perspective, distribution in adult brain, implied molecular mechanisms, and developmental basis, this article further provides a detailed account of NGFs’ role in specified neurocognitive functions. Furthermore, it discusses plausible NGF-based homeostatic and adaptation mechanisms operating in the pathogenesis of neurocognitive disorders and has presents a survey of such disorders. Finally, it elaborates on current evidence and future possibilities in therapeutic applications of NGFs with an emphasis on recent research updates in drug delivery mechanisms. Conclusive remarks of the article make a strong case for plausible role of NGFs in comprehensive regulation of the neurocognitive functions and pathogenesis of related disorders and advocate that future research should be directed to explore use of NGF-based mechanisms in the prevention of implicated diseases as well as to target these molecules pharmacologically.

scholarly journals The gut microbiota and mental health

2021 ◽  
Vol 11 (9) ◽  
pp. 304-309
Author(s):  
Sara Moqbil ◽  
Sylwiusz Niedobylski ◽  
Katarzyna Laszczak ◽  
Konrad Warchoł ◽  
Eryk Mikos
Keyword(s):  
Mental Health ◽  
Nervous System ◽  
Gut Microbiota ◽  
Neuropsychiatric Disorders ◽  
Well Being ◽  
Psychiatric Research ◽  
The Central Nervous System ◽  
Important Field ◽  
System 1

INTRODUCTION AND PURPOSE Recent studies have shown that changes in the microbiome, probiotic and antibiotic supplementation, can significantly modulate various forms of neuropsychiatric disorders - such as depression, anxiety and stress-related disorders. There is growing body of evidence pointing to a bidirectional correlation along the brain-gut microbiota line. This axis is connected through endocrine, immune and neuronal pathways. The nerves that make up the enteric nervous system transmit modifications occurring in the gastrointestinal tract and through the vagus nerve to the central nervous system (1). The main purpose of this review is to update recent information on the correlation between the gut microbiota and mental health.  STATE OF KNOWLEDGE Interactions between the gastrointestinal system and brain function have become an important field of psychiatric research in recent years. Probiotics are thought to be a potentially valuable player in the treatment of many neuropsychiatric disorders. However, the role of specific gut microbiota species in the development of these disorders remains unclear. CONCLUSIONS Increasing knowledge of the correlation between gut microbiota and mental health may improve the quality of treatment for patients with neuropsychiatric conditions. Further research on larger groups is needed to assess whether probiotics can modify altered psychological well-being and be integrated into current, conventional treatments.

Role of Prostaglandins in Multiple Sclerosis

2020 ◽  
Vol 26 (7) ◽  
pp. 730-742
Author(s):  
Surendra Gulla ◽  
Dakshayani Lomada ◽  
Anusha Lade ◽  
Reddanna Pallu ◽  
Madhava C. Reddy
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Cognitive Disability ◽  
Demyelinating Disorder ◽  
Mediators Of Inflammation ◽  
The Central Nervous System ◽  
Lateral Sclerosis

: Multiple sclerosis (MS) is an autoimmune demyelinating disorder with chronic inflammation in the central nervous system, manifested by both physical and cognitive disability. Neuroinflammation and neurodegeneration are the phenomena that appear in the central nervous system associated with various neurodegenerative disorders, including MS, Alzheimer’s diseases, amyotrophic lateral sclerosis and Parkinson’s disease. Prostaglandins are one of the major mediators of inflammation that exhibit an important function in enhancing neuroinflammatory and neurodegenerative processes. These mediators would help understand the pathophysiology of MS as the combination of antagonists or agonists of prostaglandins receptors could be beneficial during the treatment of MS. The present review focuses on the role played by different prostaglandins and the enzymes which produced them in the etiopathogenesis of MS.

Gut microbiome-mediated epigenetic regulation of brain disorder and application of machine learning for multi-omics data analysis

Genome ◽  
2020 ◽  
pp. 1-17
Author(s):  
Harpreet Kaur ◽  
Yuvraj Singh ◽  
Surjeet Singh ◽  
Raja B. Singh
Keyword(s):  
Machine Learning ◽  
Nervous System ◽  
Gut Microbiota ◽  
Epigenetic Regulation ◽  
Omics Data ◽  
Brain Disorder ◽  
Deacetylase Inhibitor ◽  
The Central Nervous System ◽  
Host Metabolism

The gut–brain axis (GBA) is a biochemical link that connects the central nervous system (CNS) and enteric nervous system (ENS). Clinical and experimental evidence suggests gut microbiota as a key regulator of the GBA. Microbes living in the gut not only interact locally with intestinal cells and the ENS but have also been found to modulate the CNS through neuroendocrine and metabolic pathways. Studies have also explored the involvement of gut microbiota dysbiosis in depression, anxiety, autism, stroke, and pathophysiology of other neurodegenerative diseases. Recent reports suggest that microbe-derived metabolites can influence host metabolism by acting as epigenetic regulators. Butyrate, an intestinal bacterial metabolite, is a known histone deacetylase inhibitor that has shown to improve learning and memory in animal models. Due to high disease variability amongst the population, a multi-omics approach that utilizes artificial intelligence and machine learning to analyze and integrate omics data is necessary to better understand the role of the GBA in pathogenesis of neurological disorders, to generate predictive models, and to develop precise and personalized therapeutics. This review examines our current understanding of epigenetic regulation of the GBA and proposes a framework to integrate multi-omics data for prediction, prevention, and development of precision health approaches to treat brain disorders.

scholarly journals Emerging Roles for the Gut Microbiome in Lymphoid Neoplasms

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Zhuangzhuang Shi ◽  
Mingzhi Zhang
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Disease Burden ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Physiological Processes ◽  
Lymphoid Neoplasms ◽  
Promising Target ◽  
Preclinical And Clinical Studies

Lymphoid neoplasms encompass a heterogeneous group of malignancies with a predilection for immunocompromised individuals, and the disease burden of lymphoid neoplasms has been rising globally over the last decade. At the same time, mounting studies delineated a crucial role of the gut microbiome in the aetiopathogenesis of various diseases. Orchestrated interactions between myriad microorganisms and the gastrointestinal mucosa establish a defensive barrier for a range of physiological processes, especially immunity and metabolism. These findings provide new perspectives to harness our knowledge of the gut microbiota for preclinical and clinical studies of lymphoma. Here, we review recent findings that support a role for the gut microbiota in the development of lymphoid neoplasms and pinpoint relevant molecular mechanisms. Accordingly, we propose the microbiota-gut-lymphoma axis as a promising target for clinical translation, including auxiliary diagnosis, novel prevention and treatment strategies, and predicting clinical outcomes and treatment-related adverse effects of the disease in the future. This review will reveal a fascinating avenue of research in the microbiota-mediated lymphoma field.

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