The AAPS Journal

, Volume 8, Issue 3, pp E606–E621

Modulation of microglial pro-inflammatory and neurotoxic activity for the treatment of Parkinson’s disease



Parkinson’s disease (PD) is a debilitating movement disorder resulting from a progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. Molecular cloning studies have identified nearly a dozen genes or loci that are associated with small clusters of mostly early onset and genetic forms of PD. The etiology of the vast majority of PD cases remains unknown, and the precise molecular and biochemical processes governing the selective and progressive degeneration of the nigrostriatal dopaminergic pathway are poorly understood. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Studies of postmortem PD brains and various cellular and animal models of PD in the last 2 decades strongly suggest that the generation of proinflammatory and neurotoxic factors by the resident brain immune cells, microglia, plays a prominent role in mediating the progressive neurodegenerative process. This review discusses literature supporting the possibility of modulating the activity of microglia as a neuroprotective strategy for the treatment of PD.


Dopamine neuron Parkinson’s disease movement disorder microglia neuroprotection free radical 

Copyright information

© American Association of Pharmaceutical Scientists 2006

Authors and Affiliations

  1. 1.Department of Pharmacodynamics, College of Pharmacy, the McKnight Brain InstituteUniversity of FloridaGainesville

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