The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower
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The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower Mina Kolahdouzmohammadi 1,3 & Mehdi Totonchi 2,3 & Sara Pahlavan 3 Accepted: 28 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Autophagy is responsible for degradation of non-essential or damaged cellular constituents and damaged organelles. The autophagy pathway maintains efficient cellular metabolism and reduces cellular stress by removing additional and pathogenic components. Dysfunctional autophagy underlies several diseases. Thus, several research groups have worked toward elucidating key steps in this pathway. Autophagy can be studied by animal modeling, chemical modulators, and in vitro disease modeling with induced pluripotent stem cells (iPSC) as a loss-of-function platform. The introduction of iPSC technology, which has the capability to maintain the genetic background, has facilitated in vitro modeling of some diseases. Furthermore, iPSC technology can be used as a platform to study defective cellular and molecular pathways during development and unravel novel steps in signaling pathways of health and disease. Different studies have used iPSC technology to explore the role of autophagy in disease pathogenesis which could not have been addressed by animal modeling or chemical inducers/inhibitors. In this review, we discuss iPSC models of autophagy-associated disorders where the disease is caused due to mutations in autophagy-related genes. We classified this group as “primary autophagy induced defects (PAID)”. There are iPSC models of diseases in which the primary cause is not dysfunctional autophagy, but autophagy is impaired secondary to disease phenotypes. We call this group “secondary autophagy induced defects (SAID)” and discuss them.
Keywords Autophagy . iPSC . Primary autophagy induced defects . Secondary autophagy induced defects Abbreviations 5AdC 5-aza-20-deoxycytidine 3-MA 3-methyladenine AD Alzheimer’s disease ADPKD Autosomal dominant polycystic kidney disease ALP Autophagy-lysosome pathway ALS Amyotrophic lateral sclerosis ANP Atrial natriuretic peptide * Mehdi Totonchi [email protected] * Sara Pahlavan [email protected] 1
Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
2
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
3
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Sq., Banihashem St., Resalat Highway, P.O. Box: 16635-148 Tehran, Iran
APP ASM ATAD3A AVs Aβ BCD BNP BVVL C9ORF72 CCCP CHMP2B CM CMA CMT CYP4V2 DA DBA DCM DHCR7 DRP1 ER
Amyloid-β precursor protein Acid sphingomyelinase AAA-domain containing protein 3A Autophagic vacuoles Amyloid beta Bietti’s crystalline dystrophy Brain natriuretic peptide Brown-Vialetto-Van Laere syndrome Chromosome 9 open
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