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Open AccessArticle

Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics

1
Biology Department, Concordia University, Montreal, QC H4B 1R6, Canada
2
Département de Chimie, Université de Montréal, Montreal, QC H3T 1J4, Canada
*
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(4), 82; https://doi.org/10.3390/biomedicines7040082
Received: 21 September 2019 / Revised: 11 October 2019 / Accepted: 15 October 2019 / Published: 18 October 2019
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited malady affecting 12.5 million people worldwide. Therapeutic options to treat PKD are limited, due in part to lack of precise knowledge of underlying pathological mechanisms. Mimics of the second mitochondria-derived activator of caspases (Smac) have exhibited activity as antineoplastic agents and reported recently to ameliorate cysts in a murine ADPKD model, possibly by differentially targeting cystic cells and sparing the surrounding tissue. A first-in-kind Drosophila PKD model has now been employed to probe further the activity of novel Smac mimics. Substantial reduction of cystic defects was observed in the Malpighian (renal) tubules of treated flies, underscoring mechanistic conservation of the cystic pathways and potential for efficient testing of drug prototypes in this PKD model. Moreover, the observed differential rescue of the anterior and posterior tubules overall, and within their physiologically diverse intermediate and terminal regions implied a nuanced response in distinct tubular regions contingent upon the structure of the Smac mimic. Knowledge gained from studying Smac mimics reveals the capacity for the Drosophila model to precisely probe PKD pharmacology highlighting the value for such critical evaluation of factors implicated in renal function and pathology. View Full-Text
Keywords: renal cystogenesis; Drosophila; disease models; Smac mimicry; polycystic kidney disease; azapeptide renal cystogenesis; Drosophila; disease models; Smac mimicry; polycystic kidney disease; azapeptide
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MDPI and ACS Style

Millet-Boureima, C.; Chingle, R.; Lubell, W.D.; Gamberi, C. Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics. Biomedicines 2019, 7, 82.

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