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Open AccessArticle

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

1
Science and Research Center, Seoul National University College of Medicine, Seoul 03080, Korea
2
Department of Neurology, Sorokdo National Hospital, Jeollanam-do 59562, Korea
3
Department of Food Science, KyungHee University College of Life Science, Seoul 17104, Korea
4
Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA
5
Department of Food Engineering, Food Safety Laboratory, Memory Unit, Ewha Womans University, Seoul 03670, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 5953; https://doi.org/10.3390/ijms21175953
Received: 8 July 2020 / Revised: 13 August 2020 / Accepted: 17 August 2020 / Published: 19 August 2020
(This article belongs to the Special Issue Role for the Enzyme Myeloperoxidase to Elicit Pathologies)
The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor. View Full-Text
Keywords: AD; Alzheimer’s disease; DDS; 4,4′-diaminodiphenyl sulfone (dapsone); LL; lepromatous leprosy (also known as Hansen’s disease); MADDS; monoacetyldapsone; NLRP3; NACHT, LRR and PYD domains-containing protein 3; MPO; myeloperoxidase; TLR; toll-like receptor AD; Alzheimer’s disease; DDS; 4,4′-diaminodiphenyl sulfone (dapsone); LL; lepromatous leprosy (also known as Hansen’s disease); MADDS; monoacetyldapsone; NLRP3; NACHT, LRR and PYD domains-containing protein 3; MPO; myeloperoxidase; TLR; toll-like receptor
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MDPI and ACS Style

Lee, J.-H.; An, H.K.; Sohn, M.-G.; Kivela, P.; Oh, S. 4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor. Int. J. Mol. Sci. 2020, 21, 5953.

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