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.
基金
funded by the Basic Science Research Program of the National Research Foundation of Korea(NRF)
which is funded by the Ministry of Science,ICT&Future Planning(NRF-2018R1D1A3B07041059 to M.M.and NRF-2016R1A5A2012284 to Y.-M.R)
by the Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01428603)
Rural Development Administration,Republic of Korea
by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)
funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HF21C0021).
