Age-primed microglia hypothesis of Parkinson's disease. Microglia functions differentially in the substantia nigra of the young (left) and aged (right) brain. Left: When facing pathogenic stimuli (large black dots), the healthy microglia in the young brain respond by releasing neurotrophic factors (small yellow dots) to support the endangered dopaminergic neurons and limit neuronal damages. Right: In the aged brain the microglia are primed with aging and function abnormally. When exposed to pathogenic stimuli, they are overactivated and release excessive oxidative stress and inflammatory factors (small black dots), which damage the vulnerable dopaminergic neurons and eventually lead to neurodegeneration.