Fig. 1

Potential mechanisms of the association of H. pylori infection with PD. (A) H. pylori virulence factors, such as LPS, CagA, VacA, and CGs, activate NF-kB or PI3K-AKT pathway to induce the production of pro-inflammatory factors of the T cells, which further stimulate glial cells, leading to neuronal injury. (B) VacA monomers assemble into oligomers and then translocate to the membranes of LEs, facilitating the entry of chloride ions into the lumen, which in turn enhances the activity of v-ATPase proton pump and reduces the intraluminal pH. Additionally, VacA induces apoptosis of epithelial cells that leads to “leaky gut” and increases the permeability of the blood-brain barrier, eventually impact nerve cells. (C) H. pylori infection cause SIBO, leading to the impairment of mitochondrial function and subsequent hindrance of ATP production and calcium influx, which are crucial for maintaining neuronal activity. Moreover, its virulence factor, VacA, can enter mitochondria and stimulate the release of cytochrome c from these organelles, further leading to mitochondrial impairment. Abbreviations: PD: Parkinson’s disease; CagA: Cytotoxin-related gene A; VacA: Vacuolar cytotoxin A; Ure: Urease; LPS: Lipopolysaccharide; TLR4: Toll-like receptor 4; LBP: Lipopolysaccharide binding protein; CG: Cholesterol glucosides; LEs: Late endonuclear bodies