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

Abstract

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.

The Preventive and Treatment of the Neuro-Inflammasome in Sorokdo National Hospital

“…(Fig. 5) DDS's action as a neuroin ammasome competitor 12 can be conjectured by comparing the AD prevalence in leprosy patients who have been prescribed DDS and those who have not. Thus, DDS is a neuroin ammasome competitor because of low AD prevalence.…”

The Preventive and Treatment of the Neuro-Inflammasome in Sorokdo National Hospital

“…So naming is Soon, Joe's treatment 31 . Dapsone may also be used to prevent, treat AD and COVID-19 ARDS 12,31 .…”

“…12 can be conjectured by comparing the AD prevalence in HD patients who have been prescribed DDS and those who have not. Thus, DDS appears to be a neuro-in ammasome competitor.…”

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

“…By what specific intracellular mechanism of action dapsone reduces neutrophils’ pro-inflammation behavior has not been established fully, but inhibition of neutrophils’ myeloperoxidase seems to be important [ 79 ]. Myeloperoxidase catalyzes the reaction: H 2 O 2 + Cl − = H 2 O + OCl − .…”