Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications

Translational Neurodegeneration

Sung-Min Kim¹  In Duk Jung¹  Yeong-Min Park²  Hyeon soo Kim³  Yong Ho Park³  Soo Jung Shin³  Kang won Lee³  Yunkwon Nam³  Chae won Kim³  Sujin Kim⁴  Minho Moon⁴  Hyun Duk Yang⁵ 

[1] Dandi Bioscience Inc, 6th Floor of Real Company Building, 66, Achasan-ro, Sungdong-gu, Seoul, Republic of Korea;Dandi Bioscience Inc, 6th Floor of Real Company Building, 66, Achasan-ro, Sungdong-gu, Seoul, Republic of Korea;Department of Immunology, School of Medicine, Konkuk University, 268, Chungwondaero, Chungju-si, Chungcheongbuk-do, Republic of Korea;Department of Biochemistry, College of Medicine, Konyang University, 35365, Daejeon, Republic of Korea;Department of Biochemistry, College of Medicine, Konyang University, 35365, Daejeon, Republic of Korea;Research Institute for Dementia Science, Konyang University, 35365, Daejeon, Republic of Korea;Harvard Neurology Clinic, 294 Gwanggyojungang-ro, Suji-gu, 16943, Yongin, Republic of Korea;

关键词: Alzheimer’s disease;    Gram-negative bacteria;    Lipopolysaccharide;    Exotoxin;    Amyloid beta;    Tau;   

DOI  :  10.1186/s40035-021-00273-y

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY