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The possible modulatory role of an angiotensin metabolite in a Parkinson model in rats /

Mostafa Adel Mohamed Elzuhary Abdelhamed Rabie

The possible modulatory role of an angiotensin metabolite in a Parkinson model in rats / الدور المعدل المحتمل لأحد المنتجات الايضية للانجيوتنسن في نموذج الشلل الرعاش بالجرذان Mostafa Adel Mohamed Elzuhary Abdelhamed Rabie ; Supervised Dalaal Moustafa Abdallah , Hanan Salah Eldin Elabhar , Noha Nagah Nassar - Cairo : Mostafa Adel Mohamed Elzuhary Abdelhamed Rabie , 2018 - 172 P. : charts , facsimiles ; 25cm

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinsons disease (PD) remains elusive. Intra-striatal post-administration of Ang 1-7 using a 6-hydroxydopamine (OHDA) PD model improved motor performance and muscle coordination. Ang 1-7 also enhanced substantia nigral tyrosine hydroxylase (TH) immunoreactivity and striatal dopamine content indicating the preservation of the dopaminergic neurons. On the molecular level, Ang 1-7 increased striatal STAT-3 and SOCS3 and MASR mRNA with the upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB. This effect extended to inhibit the striatal expression of Ang II type-1 receptor (AT-1R), RAGE, and HMGB-1, in addition to reduction in PARP-1. Ang 1-7 was also able to decrease p-MAPK p38/NF-mB p65/TNF-Ü, as well as NADPH oxidase (Nox) and lipid peroxidation to level the inflammatory and oxidative stress events off. The Ang 1-7-mediated activation of MASR cue and the suppression of the AT-1R cascade were partially reversed by the intrastartial injection of A 779, a MASR antagonist



A 779 Dopamine NADPH oxidase