Lee Jong Hoon, Kanwar Badar, Lee Chul Joong, Sergi Consolato, Coleman Michael D
Science and Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pulmonary Critical Care Medicine, Hunt Regional Hospital, Greenville, TX, USA.
iScience. 2022 Apr 20;25(5):104274. doi: 10.1016/j.isci.2022.104274. eCollection 2022 May 20.
Brain inflammation generally accelerates neurodegeneration. Alzheimer's disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD. They were treated with dapsone (4,4'-diaminodiphenyl sulfone, DDS) as a neuroinflammasome competitor and cGAS/STING pathway inhibitor. Four groups were defined: Treatment (T) 1: DDS prescribed AD diagnosed, T 2: DDS prescribed AD undiagnosed, T 3 DDS unprescribed AD diagnosed, and T 4: DDS unprescribed AD undiagnosed. Dapsone effects on AD can be clearly distinguished according to dapsone presence or absence. T1:T3 proved that the incidence of AD was significantly reduced by dapsone. T2:T3 proved that the prevalence of AD was significantly high without dapsone. T1:T4 proved that the prevalence decreased when taking dapsone. Our study demonstrates that dapsone can prevent AD exacerbation and may represent a preventive therapeutic option for exacerbated AD.
脑炎症通常会加速神经退行性变。阿尔茨海默病(AD)通过激活胞质DNA传感器环磷酸鸟苷-腺苷酸合成酶(cGAS)/干扰素基因刺激因子(STING)信号通路引发先天性免疫反应。我们的研究对麻风病患者和AD患者进行了调查。他们接受了氨苯砜(4,4'-二氨基二苯砜,DDS)治疗,氨苯砜作为一种神经炎性小体竞争剂和cGAS/STING通路抑制剂。定义了四组:治疗组(T)1:开具了氨苯砜的已确诊AD患者,T 2:开具了氨苯砜的未确诊AD患者,T 3:未开具氨苯砜的已确诊AD患者,以及T 4:未开具氨苯砜的未确诊AD患者。根据氨苯砜的有无,氨苯砜对AD的影响可以明显区分。T1:T3证明氨苯砜可显著降低AD的发病率。T2:T3证明在没有氨苯砜的情况下AD的患病率显著更高。T1:T4证明服用氨苯砜时患病率降低。我们的研究表明,氨苯砜可以预防AD病情加重,可能是一种针对病情加重的AD的预防性治疗选择。