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

NEUROBIOLOGY OF DISEASE

卷:127

Article

Lund, B. T.¹  Stone, R.^2,5  Levy, A. M.¹  Lee, S.¹  Amundson, E.¹  Kashani, N.¹  Rodgers, K. E.^3,4  Kelland, E. E.¹ 

[1] Univ Southern Calif, Keck Sch Med, Dept Neurol, 1333 San Pablo St, Los Angeles, CA 90033 USA

[2] Univ Southern Calif, Sch Pharm, Grad Program, Los Angeles, CA USA

[3] Univ Southern Calif, Sch Pharm, Titus Family Dept Clin Pharm, Los Angeles, CA USA

[4] Univ Arizona Hlth Sci, Ctr Innovat Brain Sci, Coll Med, Dept Pharmacol, Tucson, AZ USA

[5] Univ Southern Calif, Keck Med USC Specialty Pharm, Multiple Sclerosis, Los Angeles, CA USA

关键词: Experimental autoimmune encephalomyelitis;    Multiple sclerosis;    Angiotensin 1-7;    Immune infiltration;    Demyelination;    Axonal damage;    Oxidative stress;   

DOI  :  10.1016/j.nbd.2019.02.018

来源: Elsevier

【 摘 要 】

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.

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