Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
Research Institute for Dementia Science, Konyang University, Daejeon, 35365, Republic of Korea.
Transl Neurodegener. 2021 Dec 7;10(1):49. doi: 10.1186/s40035-021-00273-y.
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.
阿尔茨海默病（AD）是最严重的与年龄相关的神经退行性疾病，可导致破坏性和不可逆转的认知能力下降。针对淀粉样蛋白-β（Aβ）和 tau 的治疗靶点的开发失败，tau 是 AD 中诱导病理的主要蛋白，这表明需要向开发新的治疗靶点的范式转变。革兰氏阴性菌和脂多糖（LPS）是治疗 AD 的有吸引力的新靶点。令人惊讶的是，AD 患者中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 已被证明可影响多种与 AD 相关的病理，如 Aβ 稳态、tau 病理学、神经炎症和神经退行性变。此外，针对革兰氏阴性菌或革兰氏阴性菌分子的治疗方法显著缓解了 AD 相关的病理和认知功能障碍。尽管有多项证据表明革兰氏阴性菌及其 LPS 在 AD 发病机制中发挥关键作用，但革兰氏阴性菌及其 LPS 的致病机制尚未阐明。在这里，我们总结了革兰氏阴性菌及其 LPS 在 AD 中的作用和发病机制。此外，我们还讨论了将革兰氏阴性菌和革兰氏阴性菌分子作为 AD 治疗的新靶点和新病理特征的可能性。
