Fig. 5

Role of extracerebral-derived EVs in pathogenesis of NDDs. This schematic delineates the dualistic influence of extracerebral-derived EVs on the progression of NDDs. In physiologically normal conditions, EVs originating from peripheral tissues such as bone, adipose, and the gut microbiome are instrumental in safeguarding cerebral function. Conversely, during pathological states like OP, metabolic syndrome, and gut dysbiosis, these extracerebral EVs facilitate a perturbation of the peripheral-brain axis. Such disturbances are implicated in neuronal attrition, degenerative changes, accumulation of neurotoxic species, and heightened neuroinflammatory responses, cumulatively exacerbating the pathogenesis of NDDs