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DUOX1 in mammalian disease pathophysiology

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Abstract

Dual oxidase 1 (DUOX1) is a member of the protein family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. DUOX1 has several normal physiological, immunological, and biochemical functions in different parts of the body. Dysregulated oxidative metabolism interferes with various disease pathologies and numerous therapeutic options are based on targeting cellular redox pathways. DUOX1 forms an important enzymatic source of biological oxidants, and DUOX1 expression is frequently dysregulated in various diseases. While this review shortly addresses the biochemical and cellular properties and proposed physiological roles of DUOX1, its main purpose is to summarize the current knowledge with respect to the potential role of DUOX1 enzyme in disease pathology, especially in mammalian organisms. Although DUOX1 is normally prominently expressed in epithelial lineages, it is frequently silenced in epithelial-derived cancers by epigenetic mechanisms. While an abundance of information is available on DUOX1 transcription in different diseases, an increasing number of mechanistic studies indicate a causative relationship between DUOX1 function and disease pathophysiology. Additionally, specific functions of the DUOX1 maturation factor, DUOXA1, will also be addressed. Lastly, urgent and outstanding questions on the field of DUOX1 will be discussed that could provide valuable new diagnostic tools and novel therapeutic options.

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Abbreviations

DUOX1:

Dual oxidase 1

NOX:

NADPH oxidase

ROS:

Reactive oxygen species

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Funding

This work was supported by funds provided by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (1R01AI146857-A01 and 1R21AI147097-01A1 to B. Rada).

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Authors and Affiliations

  1. Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

    Nuha Milad Ashtiwi, Demba Sarr & Balázs Rada

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  1. Nuha Milad Ashtiwi
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  2. Demba Sarr
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  3. Balázs Rada
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N.M.A wrote and reviewed the manuscript; D.S. generated the figure and reviewed the manuscript; B.R. acquired funding, conceptualized, and reviewed the manuscript.

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Correspondence to Balázs Rada.

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Ashtiwi, N.M., Sarr, D. & Rada, B. DUOX1 in mammalian disease pathophysiology. J Mol Med 99, 743–754 (2021). https://doi.org/10.1007/s00109-021-02058-2

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  • DOI: https://doi.org/10.1007/s00109-021-02058-2

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