阿尔兹海默症口腔病原体感染假说的研究进展

Progress on the hypothesis that infection of oral pathogens triggered Alzheimer′s disease

阿尔兹海默症(Alzheimer′s disease,AD)是一种慢性神经退行性疾病.迄今为止,已经有较多关于AD发病机制的报道,但是尚未发现确切有效的治疗药物.近年来,研究者相继在AD患者脑中检测到口腔病原体,并据此提出了口腔病原体感染引发AD的假说.从机制上来说,口腔病原体侵入脑后,病原体脂多糖(lipopolysaccharide,LPS)、外膜囊泡(outer membrane vesicles,OMV)或其代谢产物引起脑区胶质细胞活化和神经发炎,从而导致神经元变性及β-淀粉样蛋白(amyloid-protein,Aβ)沉积.重要的是,靶向AD相关口腔病原体的抗菌和抗病毒药物对于AD具有潜在疗效.综合该方面的最新研究进展,讨论了口腔病原体感染如何与AD发病相关联及抗菌药物用于AD治疗的潜在应用前景.

Alzheimer′s disease(AD)was usually regarded as a chronic neurodegenerative disease.The accumulating studies focused on the pathophysiology of AD so far.However,no effective therapeutic drugs were found.During the past few years,some oral pathogens detected in the brains of AD patients,which raised hypothesis that infection of oral pathogens triggered AD.Mechanistically,oral pathogens invaded the brain where lipopolysaccharide(LPS),outer membrane vesicles(OMVs)or metabolites of oral pathogens induced glial cell activation and neuroinflammation,ultimately led to neuronal degeneration and amyloidβ-protein(Aβ)deposition.Importantly,some antibacterial and antiviral drugs targeting AD-associated oral pathogens emerged as a promising therapeutic strategy for AD.It was summarized recent advances on this topic with discussion about how oral pathogens link with pathophysiology of AD and the potential application of antimicrobial agents in the treatment of AD.