Pathogenic Modulation of Organelle Crosstalk in Helicobacter pylori-Associated Neurodegeneration

Abstract

Neurological disorders are increasingly linked to dysfunction of key cellular organelles, including mitochondria, endoplasmic reticulum (ER), lysosomes, endosomes, and peroxisomes. These organelles coordinate essential neuronal processes via tightly regulated crosstalk. Disruption in one organelle can propagate dysfunction across others, amplifying neurodegenerative cascades. Emerging evidence suggests that neurological diseases can result not only from disturbances in brain homeostasis but also from imbalances in gut homeostasis, highlighting the significant role of the gut-brain axis in maintaining neurological health. Helicobacter pylori, a gut pathogen contribute to the progression of neurological modalities by its secretome comprising Vac A, CagA, urease, and outer membrane vesicles via perturbing organelle function. These virulence factors induce mitochondrial fragmentation, ER stress, lysosomal dysfunction, and impaired mitophagy, disrupting organelle networks and promoting synaptic loss and neuronal death. Understanding how pathogen-induced organelle stress contributes to neurodegeneration offers novel insights into infection-driven brain disorders. © 2026 American Chemical Society