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Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways

INSERM, CNRS, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, University Bordeaux, 33076 Bordeaux, France
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Int. J. Mol. Sci. 2020, 21(4), 1493; https://doi.org/10.3390/ijms21041493
Received: 27 January 2020 / Revised: 17 February 2020 / Accepted: 19 February 2020 / Published: 21 February 2020
(This article belongs to the Special Issue Protein Folding and Misfolding ---- Structure and Functions)
Human cells express large amounts of different proteins continuously that must fold into well-defined structures that need to remain correctly folded and assemble in order to ensure their cellular and biological functions. The integrity of this protein balance/homeostasis, also named proteostasis, is maintained by the proteostasis network (PN). This integrated biological system, which comprises about 2000 proteins (chaperones, folding enzymes, degradation components), control and coordinate protein synthesis folding and localization, conformational maintenance, and degradation. This network is particularly challenged by mutations such as those found in genetic diseases, because of the inability of an altered peptide sequence to properly engage PN components that trigger misfolding and loss of function. Thus, deletions found in the ΔF508 variant of the Cystic Fibrosis (CF) transmembrane regulator (CFTR) triggering CF or missense mutations found in the Z variant of Alpha 1-Antitrypsin deficiency (AATD), leading to lung and liver diseases, can accelerate misfolding and/or generate aggregates. Conversely to CF variants, for which three correctors are already approved (ivacaftor, lumacaftor/ivacaftor, and most recently tezacaftor/ivacaftor), there are limited therapeutic options for AATD. Therefore, a more detailed understanding of the PN components governing AAT variant biogenesis and their manipulation by pharmacological intervention could delay, or even better, avoid the onset of AATD-related pathologies. View Full-Text
Keywords: Alpha 1-Antitrypsin deficiency; proteostasis; proteostasis network Alpha 1-Antitrypsin deficiency; proteostasis; proteostasis network
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MDPI and ACS Style

Karatas, E.; Bouchecareilh, M. Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways. Int. J. Mol. Sci. 2020, 21, 1493. https://doi.org/10.3390/ijms21041493

AMA Style

Karatas E, Bouchecareilh M. Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways. International Journal of Molecular Sciences. 2020; 21(4):1493. https://doi.org/10.3390/ijms21041493

Chicago/Turabian Style

Karatas, Esra; Bouchecareilh, Marion. 2020. "Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways" Int. J. Mol. Sci. 21, no. 4: 1493. https://doi.org/10.3390/ijms21041493

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