Angiotensin-Converting Enzyme 2 Activation Mitigates Behavioral Deficits and Neuroinflammatory Burden in 6-OHDA Induced Experimental Models of Parkinson’s Disease

• DOI: 10.1021/acschemneuro.1c00797
• Publication Date: 2022-05-09T19:56:11Z
• Authors: Shivangi Gupta; Virendra Tiwari; Priya Tiwari; Parul; Akanksha Mishra; Kashif Hanif; Shubha Shukla
• Keywords: Angiotensin-converting enzyme 2; Neurotoxicity

Hypertension is reported to cause major brain disorders including Parkinson's disease (PD), apart from cardiovascular and chronic kidney disorders. Considering this, for the first time, we explored effect of modulation ACE2/Ang (1-7)/MasR axis using diminazene aceturate (DIZE), an ACE2 activator, in 6-hydroxydopamine (6-OHDA) induced PD model. We found that DIZE treatment improved neuromuscular coordination locomotor deficits 6-OHDA rat Further, DIZE-mediated activation led increased tyrosine hydroxylase (TH) dopamine transporters (DAT) expression brain, indicating protection dopaminergic (DAergic) neurons neurotoxicity. Moreover, glial cells (astrocytes microglia) release neuroinflammatory mediators were attenuated by both vitro as well vivo models PD. exerted its activating produced Ang (1-7), a neuroprotective peptide. (1-7) conferred upon binding with G-protein-coupled MAS receptor upregulation cell survival proteins while downregulating apoptotic proteins. Importantly, these findings further validated A-779, MasR antagonist. The result showed A-779 reversed antioxidative anti-inflammatory effects decreasing markers. Although role pathology needs be additionally confirmed transgenic either overexpressing or knockout mice, still, our study demonstrates enhancing activity could novel approach ameliorating pathology.