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AMP-activated Protein Kinase as a Drug Target in Chronic Kidney Disease

[ Vol. 19 , Issue. 6 ]

Author(s):

Soumaya Allouch and Shankar Munusamy*   Pages 709 - 720 ( 12 )

Abstract:


Background: Chronic kidney disease (CKD) is a condition increasingly affecting millions of individuals worldwide and is ranked as the ninth leading cause of death in the United States. AMPactivated protein kinase (AMPK) is an energy sensor that plays a pivotal role in cellular homoeostasis. Deficiency in AMPK activity and autophagic signaling, and sustained activation of mammalian target of rapamycin (mTOR) signaling and endoplasmic reticulum (ER) stress have been shown to promote epithelial-to-mesenchymal transition (EMT) and renal cell apoptosis and contribute to CKD. Emerging evidences demonstrate that AMPK acts as a modulator of the aforementioned pathways that underpin the pathophysiology of CKD. Furthermore, pharmacological activators of AMPK such as metformin have been shown to exert renoprotective effects in experimental studies and improve clinical outcomes in patients with CKD.

Objective: The current review focuses on the nephroprotective effects of AMPK and its utility as a therapeutic target for the prevention and treatment of CKD.

Keywords:

AMP-activated protein kinase, apoptosis, autophagy, chronic kidney disease, endoplasmic reticulum stress, epithelial- mesenchymal transition, mammalian target of rapamycin, metformin.

Affiliation:

College of Pharmacy, Qatar University, PO Box 2713, Doha, College of Pharmacy, Qatar University, PO Box 2713, Doha

Graphical Abstract:



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