Fig. 1.

Sustained loop of neurodegeneration and inflammation in Parkinson’s disease. Parkinson’s disease (PD) gene mutations, PD-associated gene variants (PD risk), inflammatory gene single nucleotide polymorphisms (IF gene SNPs) plus environmental factors such as infection and aging can all trigger stress responses (upper, middle panel) and inflammatory responses (lower, middle panel) via mitochondrial damage (overall mitochondrial burden), protein burden (including impaired proteostasis but also impaired function) and the damage associated molecular patterns (DAMPs) as a result. Pathogen associated molecular patterns (PAMPs) also contribute to the triggering of stress and inflammatory responses. These self-supporting responses create a loop that facilitates further inflammatory signaling coupled with glial activation, production of reactive oxygen species (ROS) and changes to extracellular vesicle (EVs) release, which aggravates neuronal pathology. Disruption of the blood-brain barrier and gut-brain axis can further aggravate the self-sustained loop