PD (Parkinson's disease) is characterized by the selective and progressive loss of DA 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.
Conference Article| October 25 2007
Chronic microglial activation and progressive dopaminergic neurotoxicity
M.L. Block 1
*Neuropharmacology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, U.S.A.
†Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, PO Box 980709, Richmond, VA 23298-0709, U.S.A.
1To whom correspondence should be addressed (email firstname.lastname@example.org).
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M.L. Block, J.-S. Hong; Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem Soc Trans 1 November 2007; 35 (5): 1127–1132. doi: https://doi.org/10.1042/BST0351127
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