Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis

Autor: Eve E. Kelland, Roslynn Stone, Erika Amundson, S. Lee, Kathleen E. Rodgers, Nicole Kashani, Brett T. Lund, Alexander M Levy
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Agonist
Male
Encephalomyelitis
Autoimmune
Experimental
medicine.drug_class
Central nervous system
Axonal damage
Axonal loss
Disease
medicine.disease_cause
Neuroprotection
Proto-Oncogene Mas
Severity of Illness Index
Receptors
G-Protein-Coupled
lcsh:RC321-571
Multiple sclerosis
03 medical and health sciences
Mice
0302 clinical medicine
Angiotensin 1–7
Proto-Oncogene Proteins
Medicine
Animals
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Cell Proliferation
Experimental autoimmune encephalomyelitis
Dose-Response Relationship
Drug
business.industry
medicine.disease
Peptide Fragments
Immune infiltration
030104 developmental biology
medicine.anatomical_structure
Neuroprotective Agents
Treatment Outcome
Neurology
Immunology
Disease Progression
Angiotensin I
Demyelination
business
030217 neurology & neurosurgery
Oxidative stress
Zdroj: Neurobiology of Disease, Vol 127, Iss, Pp 87-100 (2019)
Popis: Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.
Databáze: OpenAIRE
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