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 Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Marjana Brkic ◽  
Sriram Balusu ◽  
Claude Libert ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Matrix Metalloproteinases ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Pathological Conditions ◽  
Progressive Loss ◽  
Neuro Inflammation ◽  
Potential Use ◽  
Lateral Sclerosis

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

scholarly journals Common Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Rossi ◽  
Bruno Santos-Lima ◽  
Eleonora Terrabuio ◽  
Elena Zenaro ◽  
Gabriela Constantin
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Neurodegenerative Diseases ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Pharmacological Intervention

Neurodegenerative diseases are closely related to inflammatory and autoimmune events, suggesting that the dysregulation of the immune system is a key pathological factor. Both multiple sclerosis (MS) and Alzheimer's disease (AD) are characterized by infiltrating immune cells, activated microglia, astrocyte proliferation, and neuronal damage. Moreover, MS and AD share a common pro-inflammatory signature, characterized by peripheral leukocyte activation and transmigration to the central nervous system (CNS). MS and AD are both characterized by the accumulation of activated neutrophils in the blood, leading to progressive impairment of the blood–brain barrier. Having migrated to the CNS during the early phases of MS and AD, neutrophils promote local inflammation that contributes to pathogenesis and clinical progression. The role of circulating T cells in MS is well-established, whereas the contribution of adaptive immunity to AD pathogenesis and progression is a more recent discovery. Even so, blocking the transmigration of T cells to the CNS can benefit both MS and AD patients, suggesting that common adaptive immunity mechanisms play a detrimental role in each disease. There is also growing evidence that regulatory T cells are beneficial during the initial stages of MS and AD, supporting the link between the modulatory immune compartments and these neurodegenerative disorders. The number of resting regulatory T cells declines in both diseases, indicating a common pathogenic mechanism involving the dysregulation of these cells, although their precise role in the control of neuroinflammation remains unclear. The modulation of leukocyte functions can benefit MS patients, so more insight into the role of peripheral immune cells may reveal new targets for pharmacological intervention in other neuroinflammatory and neurodegenerative diseases, including AD.

Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review

2019 ◽  
Vol 18 (6) ◽  
pp. 478-490 ◽  
Author(s):  
Javier Caballero-Villarraso ◽  
María J. Jiménez-Jiménez ◽  
Begoña M. Escribano ◽  
Eduardo Agüera ◽  
Abel Santamaría ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Vitamin D ◽  
Neurodegenerative Diseases ◽  
Bibliometric Analysis ◽  
Scientific Evidence ◽  
Future Trend ◽  
Clinical Severity ◽  
Double Blind ◽  
Parkinson’S Diseases

: In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer’s and Parkinson’s diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend.

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.

scholarly journals Multiple Sclerosis: Focus on Extracellular and Artificial Vesicles, Nanoparticles as Potential Therapeutic Approaches

2021 ◽  
Vol 22 (16) ◽  
pp. 8866
Author(s):  
Domenico Nuzzo ◽  
Pasquale Picone
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Mechanisms Of Action ◽  
Brain Barrier ◽  
Therapeutic Approaches ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Ms Therapy

Multiple sclerosis (MS) is an autoimmune disease of the Central Nervous System, characterized by an inflammatory process leading to the destruction of myelin with neuronal death and neurodegeneration. In MS, lymphocytes cross the blood-brain barrier, creating inflammatory demyelinated plaques located primarily in the white matter. MS potential treatments involve various mechanisms of action on immune cells, immunosuppression, inhibition of the passage through the blood-brain barrier, and immunotolerance. Bio-nanotechnology represents a promising approach to improve the treatment of autoimmune diseases by its ability to affect the immune responses. The use of nanotechnology has been actively investigated for the development of new MS therapies. In this review, we summarize the results of the studies on natural and artificial vesicles and nanoparticles, and take a look to the future clinical perspectives for their application in the MS therapy.

Fundamental study on clarification of brain molecular pathology of Nasu-Hakola disease

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 24-26
Author(s):  
Jun-ichi Satoh
Keyword(s):  
Multiple Sclerosis ◽  
Human Brain ◽  
Clinical Research ◽  
Neurodegenerative Diseases ◽  
Molecular Pathology ◽  
Large Scale ◽  
Molecular Pathogenesis ◽  
Novel Therapies ◽  
Brain Pathology ◽  
Fundamental Study

Brain pathology expert Dr Jun-ichi Satoh, from the Department of Bioinformatics and Molecular Neuropathology of Meiji Pharmaceutical University in Tokyo, is drawing on his expertise on neurology and neuroimmunology to delve into some of the more complex diseases impacting the human brain. His knowledge and expertise have allowed him to direct his research interests to study neurodegenerative diseases, such as Alzheimer's disease (AD), and neuroinflammatory diseases, such as multiple sclerosis (MS), and the analysis of their molecular pathogenesis by using a bioinformatics approach. His current focus is on Nasu-Hakola disease (NHD), a disease whose rarity has posed significant barriers towards performing large-scale clinical research in order to understand what exactly causes this disease and develop effective novel therapies.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daekwon Bae ◽  
Ji-Young Lee ◽  
Nina Ha ◽  
Jinsol Park ◽  
Jiyeon Baek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Autoimmune Encephalitis ◽  
Selective Inhibitor ◽  
Therapeutic Effects ◽  
Treatment Regimens ◽  
Ifn Γ ◽  
Experimental Autoimmune

AbstractDespite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

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