Activation of the Protective Arm of the Renin Angiotensin System in Demyelinating Disease

AbstractThe renin angiotensin system (RAS), which is classically known for blood pressure regulation, has functions beyond this. There are two axes of RAS that work to counterbalance each other and are active throughout the body, including the CNS. The pathological axis, consisting of angiotensin II (A1-8), angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R), is upregulated in many CNS diseases, including multiple sclerosis (MS). MS is an autoimmune and neurodegenerative disease of the CNS characterized by inflammation, demyelination and axonal degeneration. Published research has described increased expression of AT1R and ACE in tissues from MS patients and in animal models of MS such as experimental autoimmune encephalomyelitis (EAE). In contrast to the pathological axis, little is known about the protective axes of RAS in MS and EAE. In other neurological conditions the protective axis, which includes A1 –7, ACE2, angiotensin II type 2 receptor and Mas receptor, has been shown to have anti-inflammatory, regenerative and neuroprotective effects. Here we show, for the first time, changes in the protective arm of RAS in both EAE and MS CNS tissue. We observed a significant increase in expression of t he protective arm during stages of disease stabilization in EAE, and in MS tissue showing evidence of remyelination. These data provide evidence that the protective arm of RAS, through both ligand and receptor expression, is associated with red...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research

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This study shows that CA are released from periventricular and subpial regions to the cerebrospinal fluid and are present in the cervical lymph nodes, into which cerebrospinal fluid drains through the meningeal lymphatic system. We also show that CA can be phagocytosed by macrophages. We conclude that CA can act as containers that remove waste products from the brain and may be involved in a mechanism that cleans the brain. Moreover, we postulate that CA may contribute in some autoimmune brain diseases, exporting brain substances that interact with the immune system, and hypothesize that CA may contain brain markers that m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Neutrophils are the first line of defense in the innate immune system, helping to maintain tissue homeostasis as well as eliminating pathogens and self-components. The traditional view of neutrophils as simple phagocytes has been revised over the last decade as new research reveals their unappreciated complexity. Neutrophils are phenotypically and functionally heterogeneous, allowing them to act as modulators of both inflammation and immune responses. During acute inflammation, neutrophils perform a variety of beneficial effector functions, but when inflammation is induced by injury (sterile inflammation)...
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research
In conclusion, our results demonstrated that CXCR2 antagonism efficiently promoted OPC differentiation and enhanced remyelination in CPZ-intoxicated mice, supporting CXCR2 as a promising therapeutic target for the treatment of chronic demyelinating diseases such as MS. PMID: 31678404 [PubMed - as supplied by publisher]
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Abstract Previous studies have shown that Huangqi glycoprotein (HQGP) has an anti-inflammatory effect in vitro, and suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, the mechanism underlying its effect is largely unknown. In this manuscript we investigated the mechanisms by which HQGP protect mice from EAE. HQGP was extracted from Astragalus membranaceus and purified by anion-exchange and gel filtration chromatography. HQGP delayed disease onset, reduced disease severity and alleviated inflammation and demyelination in the central nervous system (CNS). More...
Source: Folia Neuropathologica - Category: Pathology Authors: Tags: Folia Neuropathol Source Type: research
Publication date: Available online 2 September 2019Source: Life SciencesAuthor(s): Sahar Rostami Mansoor, Ebrahim Zabihi, Maryam Ghasemi-KasmanAbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). In attempt to identify an appropriate treatment for improving the neurological symptoms and remyelination process, autologous and allogenic transplantation of mesenchymal stem cells (MSCs) have been introduced as an effective therapeutic strategy in MS. MSCs are a heterogeneous subset of pluripotent non-hematopoietic stromal cells that are isolated from bone marrow, adip...
Source: Life Sciences - Category: Biology Source Type: research
Authors: Rivera FJ, Hinrichsen B, Silva ME Abstract Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that affects the central nervous system (CNS), particularly, in young adults. Current MS treatments aim to reduce demyelination; however, these have limited efficacy, display side effects and lack of regenerative activities. Oligodendrocyte progenitor cells (OPCs) represents the major source for new myelin. Upon demyelination, OPCs get activated, proliferate, migrate towards the lesion, and differentiate into remyelinating oligodendrocytes. Although myelin repair (remyelination) represents...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the infiltration of mononuclear cells into the CNS and a subsequent inflammation of the brain. Monocytes are implicated in disease pathogenesis not only in their function as potential antigen-presenting cells involved in the local reactivation of encephalitogenic T cells but also by independent effector functions contributing to structural damage and disease progression. However, monocytes also have beneficial effects as they can exert anti-inflammatory activity and promote tissue repair. Glucocorticoids (GCs) are widely ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: [11C]MeDAS-PET and 3-[18F]-4-AP-PET imaging are well correlated, which can be used for cross-validation for imaging of demyelination in the spinal cord.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science (Neurosciences) Posters Source Type: research
Conclusion Although GWAS contributed insight into the utility of the genotype biomarker to treatment selection, adequately powered prospective studies will be required before clinical application of pharmacogenomics can become a reality. Genotype and phenotype assessment should be facilitated by the availability of detailed molecular analyses and data integration. Careful assessment of prospective GWAS data is essential to integrate findings into the clinical decision-making process, and thereby optimizing the treatment of patients with psoriasis in the future. Author Contributions BY, NG, and WY performed the project. ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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