Chronic microglial activation and progressive dopaminergic neurotoxicity

M. L. Block, J. S. Hong

Research output: Contribution to journalArticle

219 Scopus citations

Abstract

PD (Parkinson's disease) is characterized by the selective and progressive loss of OA neurons (dopaminergic neurons) in the substantia nigra. Inflammation and activation of microglia, the resident innate immune cell in the brain, have been strongly linked to neurodegenerative diseases, such as PD. Microglia can respond to immunological stimuli and neuronal death to produce a host of toxic factors, including cytokines and ROS (reactive oxygen species). Microglia can also become persistently activated after a single stimulus and maintain the elevated production of both cytokines and ROS, long after the instigating stimulus is gone. Current reports suggest that this chronic microglial activation may be fuelled by either dying/damaged neurons or autocrine and paracrine signals from local glial cells, such as cytokines. Here, we review proposed mechanisms responsible for chronic neuroinflammation and explain the interconnected relationship between deleterious microglial activation, DA neuron damage and neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)1127-1132
Number of pages6
JournalBiochemical Society Transactions
Volume35
Issue number5
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Keywords

  • Dopaminergic neuron
  • Microglia
  • NADPH oxidase
  • Neuroinflammation
  • Parkinson's disease
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

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