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

Author(s):  
Jong-hoon Lee ◽  
Chul Joong Lee ◽  
Jungwuk Park ◽  
So Jeong Lee ◽  
Su-Hee Choi ◽  
...  

Abstract Aim/Background: This study investigated patients with Alzheimer's disease (AD) treated with 4,4’-diaminodiphenyl sulfone (DDS) as a neuro-inflammasome competitor. Method: The Seoul study analyzed AD, and anti-AD drugs (AADs) in the Sorokdo National Hospital's EDI database archived from January 2005 to June 2020 through the ICD-9 and -10 codes. Result: DDS acts as a neuro-inflammasome competitor; this effect can be inferred by comparing the prevalence of AD in patients who have been prescribed DDS and those who have not. Conclusion: This study suggests the use of neuro-inflammasome therapy as a preventive and therapeutic method for AD.

2020 ◽  
Vol 21 (17) ◽  
pp. 5953
Author(s):  
Jong-hoon Lee ◽  
Ha Kyeu An ◽  
Mun-Gi Sohn ◽  
Paul Kivela ◽  
Sangsuk Oh

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.


Author(s):  
Jong-hoon Lee ◽  
Chul Joong Lee ◽  
Jungwuk Park ◽  
So Jeong Lee ◽  
Su-hee Choi

<b><i>Aim/Background:</i></b> This review investigated a patient with Alzheimer’s disease (AD) treated with 4,4’-diaminodiphenyl sulfone (DDS) as a neuroinflammasome competitor. <b><i>Methods:</i></b> We monitored AD’s progression through numeric clinical staging (NCS) with a new biomarker. NCS was determined by the presence of AD symptoms and neuropsychiatric (NP) symptoms caused by anti-AD (AAD) drugs (D) as a biomarker. We also monitored the function of DDS for stroke in a no-intake emergency state. <b><i>Results:</i></b> By introducing (D), AD’s progression was monitored through NCS staging. AAD side effects and neuropsychiatric symptoms were identified. DDS was stopped in patients with stroke with NCS 6 caused by AAD, and it rapidly proceeded to cerebral infarct. <b><i>Conclusions:</i></b> AAD can occasionally exacerbate AD and stroke. DDS can alleviate mild cognitive impairment (MCI), early AD and stroke. We clinically confirmed the role of DDS as a neuroinflammasome competitor after stroke. DDS preserved neuronal survival within 24–55 h in the Seoul Study cohort.


2021 ◽  
Author(s):  
Jong-hoon Lee

Aim/Background: This Review investigated a patient with Alzheimer’s disease (AD) treated with 4,4’-diaminodiphenyl sulfone (DDS) as a neuro-inflammasome competitor.Methods: We monitored AD’s progression through Numeric Clinical staging (NCS) with a new biomarker. NCS was determined by the AD symptoms and neuropsychiatric (NP) symptoms caused by anti-AD drugs (AAD) as a biomarker (D). We also monitored the function of DDS for Stroke in a no-intake emergency state.Results: By introducing (D), AD's progression was monitored through NCS staging; AAD side effects and neuropsychiatric symptoms were distinguished. DDS was stopped in the Stroke with NCS 6 by AAD, and it rapidly proceeds to cerebral infarct.Conclusions: AADs can occasionally exacerbate AD and Stroke. DDS can alleviate mild cognitive impairment (MCI), early AD and Stroke. We clinically confirmed the role of DDS as a neuro-inflammasome competitor after Stroke. DDS keep neuronal survivals within 24 - 55 hours in the Seoul cohort.


2022 ◽  
Author(s):  
Jong Hoon Lee ◽  
Badar Kanwar ◽  
Chul Joong Lee ◽  
Consolato Sergi ◽  
Michael Coleman

Abstract This study investigated leprosy patients with Alzheimer's disease (AD) treated with dapsone (4,4’-diaminodiphenyl sulfone, DDS) as a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and neuroinflammasome competitor. We searched the Sorokdo National Hospital medical records and the National Health Insurance Service in South Korea with the International Classification of Diseases (ICD)-10 code and Electronic Data Interchange (EDI) from January 2005 to June 2020. Four groups were defined: Treatment (T) 1: DDS prescription (+) AD prevalence (+), T 2: DDS (+) AD nondiagnosed (-), T 3: DDS nonprescription (-) AD (+), T 4: DDS (-) AD (-). The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. T1 (M = 0.18, SD = 0.074):T2 (M = 0.55, SD = 0.14) and T3 (M = 0.18, SD = 0.074):T4 (M = 0.55, SD = 0.14) explain that dapsone effects on AD can be clearly distinguished according to its presence or absence.The T1:T4 and the T2:T3 test demonstrate a causal relationship in which the presence or absence of dapsone determines the onset of AD. The T1:T3 test proved that the incidence of AD was significantly reduced by dapsone. (The t-value is -23.1, p-value is < .00001, significant at p < .05) The T2:T3 test proved that the prevalence of AD was significantly high without dapsone, and without AD was increased with dapsone. (The t-value is -6.38, p-value is < .00001, significant at p < .05) AD is increased in the absence of dapsone. Our study has demonstrated that dapsone has the potential for the prevention of AD. This study indicates that dapsone is a valid preventive therapeutic for AD. KEYWORD: Neuroinflmmasome, Alzheimer's disease, Dapsone


2020 ◽  
Author(s):  
Jong-hoon Lee ◽  
Ha Kyeu An ◽  
Mun-Gi Sohn ◽  
Paul Kivela ◽  
Sangsuk Oh

The aim of this study was 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 causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 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, TLR-Arg677Trp 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.


2021 ◽  
Author(s):  
JONG HOON LEE ◽  
Chul Joong Lee ◽  
Jungwuk Park ◽  
So Jeong Lee ◽  
Su-hee Choi

Abstract Aim/Background: This Review investigated a patient with Alzheimer’s disease (AD) treated with 4,4’-diaminodiphenyl sulfone (DDS) as a neuro-inflammasome competitor.Methods: We monitored AD’s progression through Numeric Clinical staging (NCS) with a new biomarker. NCS was determined by the AD symptoms and neuropsychiatric (NP) symptoms caused by anti-AD drugs (AAD) as a biomarker (D). We also monitored the function of DDS for Stroke in a no-intake emergency state.Results: By introducing (D), AD's progression was monitored through NCS staging; AAD side effects and neuropsychiatric symptoms were distinguished. DDS was stopped in the Stroke with NCS 6 by AAD, and it rapidly proceeds to cerebral infarct.Conclusions: AADs can occasionally exacerbate AD and Stroke. DDS can alleviate mild cognitive impairment (MCI), early AD and Stroke. We clinically confirmed the role of DDS as a neuro-inflammasome competitor after Stroke. DDS keep neuronal survivals within 24 - 55 hours in the Seoul cohort.


2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.


Author(s):  
J. Metuzals ◽  
D. F. Clapin ◽  
V. Montpetit

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.


Author(s):  
Mark Ellisman ◽  
Maryann Martone ◽  
Gabriel Soto ◽  
Eleizer Masliah ◽  
David Hessler ◽  
...  

Structurally-oriented biologists examine cells, tissues, organelles and macromolecules in order to gain insight into cellular and molecular physiology by relating structure to function. The understanding of these structures can be greatly enhanced by the use of techniques for the visualization and quantitative analysis of three-dimensional structure. Three projects from current research activities will be presented in order to illustrate both the present capabilities of computer aided techniques as well as their limitations and future possibilities.The first project concerns the three-dimensional reconstruction of the neuritic plaques found in the brains of patients with Alzheimer's disease. We have developed a software package “Synu” for investigation of 3D data sets which has been used in conjunction with laser confocal light microscopy to study the structure of the neuritic plaque. Tissue sections of autopsy samples from patients with Alzheimer's disease were double-labeled for tau, a cytoskeletal marker for abnormal neurites, and synaptophysin, a marker of presynaptic terminals.


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