Microglia-mediated neuron damage. Microglia activation has been implicated in the progressive nature of Alzheimer's disease. Microglia can become deleteriously activated in response to disease-specific stimuli (amyloid-β (Aβ) oligomers, Aβ fibrils, and senile plaques) to produce a catalogue of factors, such as reactive oxygen species and cytokines that are toxic to neurons. In addition to disease-specific pro-inflammatory stimuli, neuronal damage/death can also activate microglia to produce these toxic factors. This continual and self-perpetuating cycle of neuronal damage/death followed by microglial activation is commonly referred to as reactive microgliosis and may be an underlying mechanism of the progressive nature of diverse neurodegenerative diseases, including Alzheimer's disease. Although all forms of Aβ have yet to be tested in detail, NADPH oxidase (also called phagocytic oxidase (PHOX)) has been implicated as a key mechanism through which microglia damage neurons in response to Aβ and neuron damage/death. This figure is modified from Block et al. . NO, nitric oxide; PGE2, prostaglandin E2; TNF, tumor necrosis factor.
Block BMC Neuroscience 2008 9(Suppl 2):S8 doi:10.1186/1471-2202-9-S2-S8