Fig. 3

Inflammation in PD. Lewy bodies, mainly composed of α-synuclein aggregates, are one of the pathological features of PD. It is generally accepted that some genetic and environment factors lead to the aggregation of α-synuclein. Excessive α-synuclein in neuron is transported into the mitochondria, leading to the mitochondrial dysfunction that is central to the progression of PD. Mutations in mitochondrial-associated proteins like LRRK2, PINK1, PARK7, and PRKN, which are found in familial cases of PD, also induce mitochondrial dysfunction and lead to neurotoxicity. Excessive aggregation of α-synuclein or failure to clear it from the cell will result in its release either directly from the neuron or through the exosome, which activates microglia and amplifies neurotoxicity by spreading α-synuclein to the neighboring healthy DA neurons. DAMPs released from dying neurons further enhance the activation of microglia. In addition, genetic and environment factors also promote the activation of microglia and other immune cells. Activated microglia further exacerbate disease by enhancing α-synuclein pathogenicity, increasing oxidative stress, and promoting mitochondrial dysfunction