Figure 5.

Possible mechanism of reactive microgliosis by HNM. When neurons are damaged by neurotoxic factors, such as 1-methyl- 4-phenyl-1, 2,3, 6-tetrahydropyridine (MPTP), rotenone and paraquat, etc, signals are sent out to alert microglia so that neurons can be phagocytized. The mechanism whereby neurons signal to microglia remains unclear. Studies from our laboratory and others suggest that signals may come from two components: 1) proteins from dopaminergic neurons, such as NM, α-synuclein; 2) extracellular matrix proteins, such as metalloproteinase-3 (MMP-3), laminin, etc. These components leaked out from damaged neurons activate microglia via the activation of microglia antigen-1 (Mac-1, a receptor responsible for phagocytosis and oxidative burst) followed by the activation of PHOX (a superoxide-generating enzyme), leading to the increased production of reactive oxygen species (ROS), causing the continued death of dopaminergic neurons and formation of a self-propelling vicious cycle.