scholarly journals Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1507
Author(s):  
Soyoung Choi ◽  
Li Guo ◽  
Maria Francesca Cordeiro
Keyword(s):  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Comprehensive Understanding ◽  
Retinal Microglia ◽  
The Central Nervous System ◽  
Automated Algorithms ◽  
And Function ◽  
Exciting Area

Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS). When activated by stress stimuli, retinal microglia change their morphology and activity, with either beneficial or harmful consequences. In this review, we describe characteristics of CNS microglia, including those in the retina, with a focus on their morphology, activation states and function in health, ageing, MS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, glaucoma and retinitis pigmentosa, to highlight their activity in disease. We also discuss contradictory findings in the literature and the potential ways of reducing inconsistencies in future by using standardised methodology, e.g., automated algorithms, to enable a more comprehensive understanding of this exciting area of research.

Neuroinflammatory State of Multiple Sclerosis and Strategies for Biotherapeutics Development

2021 ◽  
Author(s):  
Samira Soltanmoradi ◽  
Fatemeh Kouhkan ◽  
Iman Rad
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Treg Cells ◽  
Progressive Multiple Sclerosis ◽  
Common Symptom ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Relapsing Remitting Multiple Sclerosis

Multiple Sclerosis (MS) is the most prevalent neurological disability in young adults. The pathogenesis of MS is characterized by demyelination and neurodegeneration in the central nervous system (CNS) as the ruinous result of chronic activation of the immune system. All clinical forms of MS, including relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), and the primary progressive MS (PPMS), demonstrate inflammation as a common symptom. In various autoimmune diseases like MS, the ability of the immune system to set a balance between pro-inflammatory and anti-inflammatory responses is lost. In this review, the imbalance between pro-inflammatory and anti-inflammatory responses of immune cells and their role in MS progression is discussed. Disturbing the balance of Th1/Th2 and Th17/Treg cells and M1/M2 phenotypes of macrophages and microglial plays a key role in the development and progression of MS. In this review, we first depict an outline of regulatory immune cells involved in inflammation. Second, we discuss shreds of evidence that confirm how B cells play both pathogenic and protective roles in MS disease. Third, we point out the pros and cons of B cell/T cell-targeted therapies in clinical trials.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

scholarly journals Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. eaav7188 ◽  
Author(s):  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Expression Profiles ◽  
Human Microglia ◽  
Histocompatibility Complex ◽  
The Central Nervous System ◽  
Reference Map ◽  
Peripheral Immune Cells ◽  
Genomic Map ◽  
Cellular Components

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

scholarly journals Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyuk Sung Kwon ◽  
Seong-Ho Koh
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Drugs ◽  
M1 Phenotype ◽  
The Central Nervous System ◽  
The Relationship ◽  
Lateral Sclerosis ◽  
M2 Phenotype

AbstractNeuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.

scholarly journals Crosstalk Between Tumor-Associated Microglia/Macrophages and CD8-Positive T Cells Plays a Key Role in Glioblastoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Tu ◽  
Xu Lin ◽  
Jili Qiu ◽  
Jiaqi Zhou ◽  
Hui Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Malignant Disease ◽  
Immune Therapy ◽  
Cell Types ◽  
Different Types ◽  
The Central Nervous System ◽  
And Function ◽  
The Relationship

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.

scholarly journals Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Cell Types ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

scholarly journals Current Understanding of Central Nervous System Drainage Systems: Implications in the Context of Neurodegenerative Diseases

2020 ◽  
Vol 18 (11) ◽  
pp. 1054-1063 ◽  
Author(s):  
Vladimir N. Nikolenko ◽  
Marine V. Oganesyan ◽  
Angela D. Vovkogon ◽  
Arina T. Nikitina ◽  
Ekaterina A. Sozonova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Lymphatic Vessels ◽  
Basal Area ◽  
Waste Products ◽  
Glymphatic System ◽  
The Central Nervous System ◽  
New Perspective ◽  
And Function

Until recently, it was thought that there were no lymphatic vessels in the central nervous system (CNS). Therefore, all metabolic processes were assumed to take place only in the circulation of the cerebrospinal fluid (CSF) and through the blood-brain barrier’s (BBB), which regulate ion transport and ensure the functioning of the CNS. However, recent findings yield a new perspective: There is an exchange of CSF with interstitial fluid (ISF), which is drained to the paravenous space and reaches lymphatic nodes at the end. This circulation is known as the glymphatic system. The glymphatic system is an extensive network of meningeal lymphatic vessels (MLV) in the basal area of the skull that provides another path for waste products from CNS to reach the bloodstream. MLV develop postnatally, initially appearing around the foramina in the basal part of the skull and the spinal cord, thereafter sprouting along the skull’s blood vessels and spinal nerves in various areas of the meninges. VEGF-C protein (vascular endothelial growth factor), expressed mainly by vascular smooth cells, plays an important role in the development of the MLV. The regenerative potential and plasticity of MLV and the novel discoveries related to CNS drainage offer potential for the treatment of neurodegenerative diseases such as dementia, hydrocephalus, stroke, multiple sclerosis, and Alzheimer disease (AD). Herein, we present an overview of the structure and function of the glymphatic system and MLV, and their potential involvement in the pathology and progression of neurodegenerative diseases.

scholarly journals Immune Responses in Neurodegenerative Diseases

2015 ◽  
Vol 12 (1) ◽  
pp. 67-76 ◽  
Author(s):  
R Shrestha ◽  
Shakya Shrestha ◽  
O Millington ◽  
J Brewer ◽  
T Bushell
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Review Article ◽  
Progressive Loss ◽  
Parkinson’S Diseases ◽  
Key Factor ◽  
Huge Impact ◽  
Diseased Condition

Neurodegenerative disease is a progressive loss of neurons from central nervous system and has a huge impact on health care system. Various causes have been proposed of which inflammation has been suggested to be a probable key factor in the most of such conditions. The involvement of immune cells including lymphocytes in such diseased condition of the CNS supports this notion. The effective therapy for these diseases has been sought for more than a half century but still lacking such therapy. On such basis this review article has mainly focussed on evidence of the involvement of immune cells in various neurodegenerative diseases including Alzheimer’s disease, Parkinson’s diseases and Multiple sclerosis and suggests a possible therapy of such diseased conditions of the CNS by the modulation of immune system.Kathmandu University Medical Journal Vol.12(1) 2014: 67-76

scholarly journals Role of Macrophages and Microglia in Zebrafish Regeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4768 ◽  
Author(s):  
Susanna R. Var ◽  
Christine A. Byrd-Jacobs
Keyword(s):  
Nervous System ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
And Function ◽  
High Degree ◽  
Human Nerve

Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.

scholarly journals Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis

2016 ◽  
Vol 397 (12) ◽  
pp. 1277-1286 ◽  
Author(s):  
Hyesook Yoon ◽  
Isobel A. Scarisbrick
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Systemic Administration ◽  
Neurological Deficits ◽  
Interleukin 17 ◽  
The Impact

Abstract Kallikrein-related peptidase 6 (Klk6) is elevated in the serum of multiple sclerosis (MS) patients and is hypothesized to participate in inflammatory and neuropathogenic aspects of the disease. To test this hypothesis, we investigated the impact of systemic administration of recombinant Klk6 on the development and progression of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). First, we determined that Klk6 expression is elevated in the spinal cord of mice with EAE at the peak of clinical disease and in immune cells upon priming with the disease-initiating peptide in vitro. Systemic administration of recombinant Klk6 to mice during the priming phase of disease resulted in an exacerbation of clinical symptoms, including earlier onset of disease and higher levels of spinal cord inflammation and pathology. Treatment of MOG35-55-primed immune cells with Klk6 in culture enhanced expression of pro-inflammatory cytokines, interferon-γ, tumor necrosis factor, and interleukin-17, while reducing anti-inflammatory cytokines interleukin-4 and interleukin-5. Together these findings provide evidence that elevations in systemic Klk6 can bias the immune system towards pro-inflammatory responses capable of exacerbating the development of neuroinflammation and paralytic neurological deficits. We suggest that Klk6 represents an important target for conditions in which pro-inflammatory responses play a critical role in disease development, including MS.

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