Grozdanov V, et al. - Researchers assessed if pathologic alpha-synuclein specifically triggers excessive inflammatory responses in Parkinson's disease. By evaluating cytokine release upon exposure, researchers explored the immune response of primary human monocytes and a microglial cell line to pathologic forms of alpha-synuclein. According to findings, a vigorous inflammatory activation of human monocytes and microglial BV2 cells results from pathological alpha-synuclein (mutations, aggregation). They also discovered that extracellular vesicles potentiate extracellular alpha-synuclein activation of immune cells, maybe by facilitating alpha-synuclein uptake. A stronger activation of monocytes is induced by blood extracellular vesicles from Parkinson's disease patients vs blood extracellular vesicles from healthy controls. In response to stimulation with pathologic alpha-synuclein, monocytes from Parkinson's disease patients are dysregulated and hyperactive. Overall, the authors concluded that monocyte dysregulation and alpha-synuclein pathology in Parkinson's disease can act together to induce excessive inflammatory responses to alpha-synuclein.