scholarly journals Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders

2020 ◽  
Vol 19 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Urvashi Langeh ◽  
Shamsher Singh
Keyword(s):  
Neurological Disorders ◽  
Calcium Binding ◽  
Mapk Pathway ◽  
Neuronal Loss ◽  
S100b Protein ◽  
Helix Loop Helix ◽  
Glycation End Products ◽  
The Central Nervous System ◽  
Therapeutic Measures

: Neurological disorders (ND) are the central nervous system (CNS) related complications originated by enhanced oxidative stress, mitochondrial failure and overexpression of proteins like S100B. S100B is a helix-loop-helix protein with the calcium-binding domain associated with various neurological disorders through activation of the MAPK pathway, increased NF-kB expression resulting in cell survival, proliferation and gene up-regulation. S100B protein plays a crucial role in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Schizophrenia and epilepsy because the high expression of this protein directly targets astrocytes and promotes neuroinflammation. Under stressful conditions, S100B produces toxic effects mediated through receptor for advanced glycation end products (AGE) binding. S100B also mediates neuroprotection, minimizes microgliosis and reduces the expression of tumor necrosis factor (TNF-alpha) but that are concentration- dependent mechanisms. Increased level of S100B is useful for assessing the release of inflammatory markers, nitric oxide and excitotoxicity dependent neuronal loss. The present review summarizes the role of S100B in various neurological disorders and potential therapeutic measures to reduce the prevalence of neurological disorders.

scholarly journals Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jiaying Wu ◽  
Yuyu Zhang ◽  
Hongyu Yang ◽  
Yuefeng Rao ◽  
Jing Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Neurological Disorders ◽  
Digestive System ◽  
Hygiene Hypothesis ◽  
Host Susceptibility ◽  
Immune Disorders ◽  
The Central Nervous System ◽  
Symbiotic Microbiota

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people’s attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Microglia in Prion Diseases: Angels or Demons?

2020 ◽  
Vol 21 (20) ◽  
pp. 7765
Author(s):  
Caterina Peggion ◽  
Roberto Stella ◽  
Paolo Lorenzon ◽  
Enzo Spisni ◽  
Alessandro Bertoli ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Normal Brain ◽  
Primary Microglia ◽  
Neuroinflammatory Response ◽  
Brain Physiology ◽  
The Central Nervous System

Prion diseases are rare transmissible neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the cellular prion protein (PrPC) in the central nervous system (CNS). Neuropathological hallmarks of prion diseases are neuronal loss, astrogliosis, and enhanced microglial proliferation and activation. As immune cells of the CNS, microglia participate both in the maintenance of the normal brain physiology and in driving the neuroinflammatory response to acute or chronic (e.g., neurodegenerative disorders) insults. Microglia involvement in prion diseases, however, is far from being clearly understood. During this review, we summarize and discuss controversial findings, both in patient and animal models, suggesting a neuroprotective role of microglia in prion disease pathogenesis and progression, or—conversely—a microglia-mediated exacerbation of neurotoxicity in later stages of disease. We also will consider the active participation of PrPC in microglial functions, by discussing previous reports, but also by presenting unpublished results that support a role for PrPC in cytokine secretion by activated primary microglia.

scholarly journals Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation

2015 ◽  
Vol 70 (6) ◽  
pp. 694-703 ◽  
Author(s):  
Yuliya Aleksandrovna Uspenskaya ◽  
Yuliya Konstantinovna Komleva ◽  
Elena Anatol'evna Pozhilenkova ◽  
Vladimir Valer'evic Salmin ◽  
Ol'ga Leonidovna Lopatina ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Advanced Glycation End Products ◽  
Calcium Binding ◽  
Advanced Glycation ◽  
Endogenous Ligands ◽  
Inflammatory Reactions ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RAGE are well-known: advanced glycation end products (AGE), amyloid-beta (Аβ), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 и S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.

scholarly journals Features of nervous system damage in antiphospholipid syndrome

2021 ◽  
Vol 15 (4) ◽  
pp. 404-414
Author(s):  
O. N. Voskresenskaya ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
T. A. Sukontseva ◽  
M. V. Tretyakova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Antiphospholipid Syndrome ◽  
Neurological Disorders ◽  
Molecular Mimicry ◽  
Transverse Myelitis ◽  
Autoimmune Process ◽  
The Central Nervous System ◽  
Interdisciplinary Interaction

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

S100B raises the alert in subarachnoid hemorrhage

2016 ◽  
Vol 27 (7) ◽  
pp. 745-759 ◽  
Author(s):  
Zhao Zhong Chong
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Calcium Binding ◽  
Intracellular Signaling ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Protein S100b ◽  
Novel Therapeutic

AbstractSubarachnoid hemorrhage (SAH) is a devastating disease with high mortality and mobility, the novel therapeutic strategies of which are essentially required. The calcium binding protein S100B has emerged as a brain injury biomarker that is implicated in pathogenic process of SAH. S100B is mainly expressed in astrocytes of the central nervous system and functions through initiating intracellular signaling or via interacting with cell surface receptor, such as the receptor of advanced glycation end products. The biological roles of S100B in neurons have been closely associated with its concentrations, resulting in either neuroprotection or neurotoxicity. The levels of S100B in the blood have been suggested as a biomarker to predict the progress or the prognosis of SAH. The role of S100B in the development of cerebral vasospasm and brain damage may result from the induction of oxidative stress and neuroinflammation after SAH. To get further insight into mechanisms underlying the role of S100B in SAH based on this review might help us to find novel therapeutic targets for SAH.

scholarly journals Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1692
Author(s):  
Baiyan Ren ◽  
Anna Dunaevsky
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Stem Cell Differentiation ◽  
Patient Specific ◽  
Human Astrocytes ◽  
Structural And Functional Properties ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
Induced Pluripotent

Accumulating studies demonstrate the morphological and functional diversity of astrocytes, a subtype of glial cells in the central nervous system. Animal models are instrumental in advancing our understanding of the role of astrocytes in brain development and their contribution to neurological disease; however, substantial interspecies differences exist between rodent and human astrocytes, underscoring the importance of studying human astrocytes. Human pluripotent stem cell differentiation approaches allow the study of patient-specific astrocytes in the etiology of neurological disorders. In this review, we summarize the structural and functional properties of astrocytes, including the unique features of human astrocytes; demonstrate the necessity of the stem cell platform; and discuss how this platform has been applied to the research of neurodevelopmental and neuropsychiatric diseases.

scholarly journals Olig2 regulates p53-mediated apoptosis, migration and invasion of melanoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji Eun Lee ◽  
Sungjin Ahn ◽  
Haengdueng Jeong ◽  
Seungchan An ◽  
Cheol Hwan Myung ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Enzyme Activity ◽  
Malignant Cell ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
High Recurrence Rate ◽  
Metastatic Progression ◽  
Helix Loop Helix ◽  
The Central Nervous System

AbstractMelanoma is a disease with a high recurrence rate and poor prognosis; therefore, the need for targeted therapeutics is steadily increasing. Oligodendrocyte transcription factor2 (Olig2) is a basic helix-loop-helix transcription factor that is expressed in the central nervous system during embryonic development. Olig2 is overexpressed in various malignant cell lines such as lung carcinoma, glioma and melanoma. Olig2 is known as a key transcription factor that promotes tumor growth in malignant glioma. However, the role of Olig2 in melanoma is not well characterized. We analyzed the role of Olig2 in apoptosis, migration, and invasion of melanoma cells. We confirmed that Olig2 was overexpressed in melanoma cells and tissues. Reduction of Olig2 increased apoptosis in melanoma cells by increasing p53 level and caspase-3/-7 enzyme activity. In addition, downregulation of Olig2 suppressed migration and invasion of melanoma cells by inhibiting EMT. Reduction of Olig2 inhibited expression of MMP-1 and the enzyme activity of MMP-2/-9 induced by TGF-β. Moreover, Olig2 was involved in the downstream stages of MEK/ERK and PI3K/AKT, which are major signaling pathways in metastatic progression of melanoma. In conclusion, this study demonstrated the crucial roles of Olig2 in apoptosis, migration, and invasion of melanoma and may help to further our understanding of the relationship between Olig2 and melanoma progression.

scholarly journals Pericytes for Therapeutic Approaches to Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Cao ◽  
Yanbo Zhou ◽  
Mengguang Chen ◽  
Li Li ◽  
Wei Zhang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neurovascular Unit ◽  
Therapeutic Approaches ◽  
Multipotent Cells ◽  
The Central Nervous System

Pericytes are perivascular multipotent cells located on capillaries. Although pericytes are discovered in the nineteenth century, recent studies have found that pericytes play an important role in maintaining the blood—brain barrier (BBB) and regulating the neurovascular system. In the neurovascular unit, pericytes perform their functions by coordinating the crosstalk between endothelial, glial, and neuronal cells. Dysfunction of pericytes can lead to a variety of diseases, including stroke and other neurological disorders. Recent studies have suggested that pericytes can serve as a therapeutic target in ischemic stroke. In this review, we first summarize the biology and functions of pericytes in the central nervous system. Then, we focus on the role of dysfunctional pericytes in the pathogenesis of ischemic stroke. Finally, we discuss new therapies for ischemic stroke based on targeting pericytes.

scholarly journals Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin P. Passaro ◽  
Abraham L. Lebos ◽  
Yao Yao ◽  
Steven L. Stice
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Disorders ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Traditional Approaches ◽  
The Impact ◽  
Neurological Pathology

Neuroinflammation is a key component of neurological disorders and is an important therapeutic target; however, immunotherapies have been largely unsuccessful. In cases where these therapies have succeeded, particularly multiple sclerosis, they have primarily focused on one aspect of the disease and leave room for improvement. More recently, the impact of the peripheral immune system is being recognized, since it has become evident that the central nervous system is not immune-privileged, as once thought. In this review, we highlight key interactions between central and peripheral immune cells in neurological disorders. While traditional approaches have examined these systems separately, the immune responses and processes in neurological disorders consist of substantial crosstalk between cells of the central and peripheral immune systems. Here, we provide an overview of major immune effector cells and the role of the blood-brain barrier in regard to neurological disorders and provide examples of this crosstalk in various disorders, including stroke and traumatic brain injury, multiple sclerosis, neurodegenerative diseases, and brain cancer. Finally, we propose targeting central-peripheral immune interactions as a potential improved therapeutic strategy to overcome failures in clinical translation.

Sign in / Sign up

Export Citation Format

Share Document