Neprilysin, the kidney brush border neutral proteinase: a possible potential target for ischemic renal injury

Sankhe, Runali and Kinra, Manas and Mudgal, Jayesh and Arora, Devinder and Nampoothiri, Madhavan (2020) Neprilysin, the kidney brush border neutral proteinase: a possible potential target for ischemic renal injury. Toxicology Mechanisms and Methods, 30 (2). pp. 88-99. ISSN 1537-6516

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Abstract

Neprilysin (NEP) is an endogenously induced peptidase for modulating production and degradation of various peptides in humans. It is most abundantly present in kidney and regulates the intrinsic renal homeostatic mechanism. Recently, drugs inhibiting NEP have been approved for the use in heart fail�ure. In the context of increased prevalence of ischemia associated renal failure, NEP could be an attractive target for treating kidney failure. In the kidney, targeting NEP may possess potential benefits as well as adverse consequences. The unfavorable outcomes of NEP are mainly attributed to the deg�radation of the natriuretic peptides (NPs). NPs are involved in the inhibition of the renin–angiotensi�n–aldosterone system (RAAS) and activation of the sympathetic system contributing to the tubular and glomerular injury. In contrary, NEP exerts the beneficial effect by converting angiotensin-1 (Ang I) to angiotensin-(1–7) (Ang-(1–7)), thus activating MAS-related G protein coupled receptor. MAS receptor antagonizes angiotensin type I receptor (AT-1R), reduces reactive oxygen species (ROS) and inflamma�tion, thus ameliorating renal injury. However, the association of NEP with complex cascades of renal ischemia remains vague. Therefore, there is a need to evaluate the putative mechanism of NEP and its overlap with other signaling cascades in conditions of renal ischemia.

Item Type: Article
Uncontrolled Keywords: Neprilysin; renal failure; peptides; RAAS; MAS receptor.
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 02 Jul 2020 04:18
Last Modified: 02 Jul 2020 04:18
URI: http://eprints.manipal.edu/id/eprint/155212

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