Microglial activation and chronic neurodegeneration

Melinda E Lull; Michelle L Block

doi:10.1016/j.nurt.2010.05.014

. 2010 Oct;7(4):354–365. doi: 10.1016/j.nurt.2010.05.014

Microglial activation and chronic neurodegeneration

Melinda E Lull ¹, Michelle L Block ^1,^✉

PMCID: PMC2951017 NIHMSID: NIHMS234040 PMID: 20880500

Summary

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype.

Key Words: Microglia, inflammation-mediated neurodegeneration, oxidative stress, chronic neurotoxicity, reactive microgliosis

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Microglial activation and chronic neurodegeneration

Melinda E Lull

Michelle L Block

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Microglial activation and chronic neurodegeneration

Melinda E Lull

Michelle L Block

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