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

Title:

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

Millet-Boureima, Cassandra ORCID: https://orcid.org/0000-0002-1521-0778, Chingle, Ramesh ORCID: https://orcid.org/0000-0003-1175-2454, Lubell, William D. ORCID: https://orcid.org/0000-0002-3080-2712 and Gamberi, Chiara ORCID: https://orcid.org/0000-0002-7122-6491 (2019) Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics. Biomedicines, 7 (4). pp. 1-17. ISSN 2227-9059

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Official URL: https://doi.org/10.3390/biomedicines7040082

Abstract

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.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Article
Refereed:Yes
Authors:Millet-Boureima, Cassandra and Chingle, Ramesh and Lubell, William D. and Gamberi, Chiara
Journal or Publication:Biomedicines
Date:18 October 2019
Digital Object Identifier (DOI):10.3390/biomedicines7040082
Keywords:renal cystogenesis; Drosophila; disease models; Smac mimicry; polycystic kidney disease; azapeptide
ID Code:986040
Deposited By: KATHARINE HALL
Deposited On:22 Oct 2019 18:39
Last Modified:22 Oct 2019 18:39
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