Gram-negative bacteria and their lipopolysaccharides in Alzheimer's disease: pathologic roles and therapeutic implications.
Gram-negative bacteria and their lipopolysaccharides in Alzheimer's disease: pathologic roles and therapeutic implications.
复制标题
DOI：
10.1186/s40035-021-00273-y
复制
发表时间：
2021-12-07
影响因子：
12.6
通讯作者：
Moon M
中科院分区：
文献类型：
--
作者：
Kim HS;Kim S;Shin SJ;Park YH;Nam Y;Kim CW;Lee KW;Kim SM;Jung ID;Yang HD;Park YM;Moon M
阿尔茨海默病（Alzheimer's disease，AD）是最严重的与年龄相关的神经退行性疾病，可引起破坏性和不可逆的认知功能下降。靶向淀粉样蛋白-β（Aβ）和tau（AD中诱导病理学的主要蛋白质）的治疗剂开发失败，表明了向开发新治疗靶点的范式转变。革兰氏阴性菌和脂多糖（LPS）是治疗AD的新靶点。令人惊讶的是，在AD患者中已经报道了革兰氏阴性菌及其LPS的分布改变。此外，革兰氏阴性菌及其LPS已显示影响多种AD相关病理，如Aβ稳态、tau病理、神经炎症和神经变性。此外，革兰氏阴性菌或革兰氏阴性菌分子为靶点的治疗方法显著缓解了AD相关的病理和认知功能障碍。尽管有证据表明革兰氏阴性菌及其脂多糖在AD发病中起着重要作用，但革兰氏阴性菌及其脂多糖的致病机制尚未阐明。现就革兰阴性菌和脂多糖在AD中的作用及发病机制作一综述。此外，我们讨论了使用革兰氏阴性菌和革兰氏阴性菌分子作为新的治疗靶点和新的病理特征的AD的可能性。在线版本包含补充材料，可通过10.1186/s40035-021-00273-y获得。
Alzheimer’s disease (AD) is the most serious age-related neurodegenerative disease and causes destructive and irreversible cognitive decline. Failures in the development of therapeutics targeting amyloid-β (Aβ) and tau, principal proteins inducing pathology in AD, suggest a paradigm shift towards the development of new therapeutic targets. The gram-negative bacteria and lipopolysaccharides (LPS) are attractive new targets for AD treatment. Surprisingly, an altered distribution of gram-negative bacteria and their LPS has been reported in AD patients. Moreover, gram-negative bacteria and their LPS have been shown to affect a variety of AD-related pathologies, such as Aβ homeostasis, tau pathology, neuroinflammation, and neurodegeneration. Moreover, therapeutic approaches targeting gram-negative bacteria or gram-negative bacterial molecules have significantly alleviated AD-related pathology and cognitive dysfunction. Despite multiple evidence showing that the gram-negative bacteria and their LPS play a crucial role in AD pathogenesis, the pathogenic mechanisms of gram-negative bacteria and their LPS have not been clarified. Here, we summarize the roles and pathomechanisms of gram-negative bacteria and LPS in AD. Furthermore, we discuss the possibility of using gram-negative bacteria and gram-negative bacterial molecules as novel therapeutic targets and new pathological characteristics for AD. The online version contains supplementary material available at 10.1186/s40035-021-00273-y.
登录
查看更多内容
反式白藜芦醇在牙龈卟啉单胞菌脂多糖挑战神经元细胞模型中的分子作用模式的评估。
影响因子：
2.8
作者：
Bahar B;Singhrao SK
通讯作者：
Singhrao SK
影响因子：
4.8
作者：
Akbari E;Asemi Z;Daneshvar Kakhaki R;Bahmani F;Kouchaki E;Tamtaji OR;Hamidi GA;Salami M
通讯作者：
Salami M
影响因子：
4.2
作者：
Balducci, Claudia;Santamaria, Giulia;Forloni, Gianluigi
通讯作者：
Forloni, Gianluigi
影响因子：
4
作者：
Beydoun, May A.;Beydoun, Hind A.;Zonderman, Alan B.
通讯作者：
Zonderman, Alan B.
影响因子：
9.3
作者：
Bachstetter, Adam D.;Xing, Bin;Van Eldik, Linda J.
通讯作者：
Van Eldik, Linda J.