Fig. 3

Alpha-synuclein and microglial Nox2 activation. The activation of microglia by alpha-synuclein can implicate several cell surface receptors such as P2X7, TLR2/4 and CR3 and subsequent activations of several kinases such as PKC, Akt, MAPKs, PAK and ERK1/2. This in turn could promote the phosphorylation and translocation of p47phox and subsequent Nox2 activation. Released oxygen species appear to promote microglia chemoattraction, activation and oxidative stress. Neuronal damage leads to the release of alpha-synuclein and the TLR-agonist high mobility group box protein 1 (HMGB1)