Microglial Activation and Chronic Neurodegeneration

Melinda E. Lull, Michelle Block

Research output: Contribution to journalArticle

416 Citations (Scopus)

Abstract

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative 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.

Original languageEnglish (US)
Pages (from-to)354-365
Number of pages12
JournalNeurotherapeutics
Volume7
Issue number4
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Microglia
Reactive Oxygen Species
Neurons
Poisons
Interleukin-1
Neurodegenerative Diseases
Parkinson Disease
Lipopolysaccharides
Nitric Oxide
Tumor Necrosis Factor-alpha
Pathology
Phenotype
Brain

Keywords

  • Chronic neurotoxicity
  • Inflammation-mediated neurodegeneration
  • Microglia
  • Oxidative stress
  • Reactive microgliosis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

Cite this

Microglial Activation and Chronic Neurodegeneration. / Lull, Melinda E.; Block, Michelle.

In: Neurotherapeutics, Vol. 7, No. 4, 10.2010, p. 354-365.

Research output: Contribution to journalArticle

Lull, Melinda E. ; Block, Michelle. / Microglial Activation and Chronic Neurodegeneration. In: Neurotherapeutics. 2010 ; Vol. 7, No. 4. pp. 354-365.
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