Parkinson's Disease

Parkinson's Disease

Molecular and Therapeutic Insights From Model Systems
2008, Pages 545-557
Parkinson's Disease

Chapter 40 - Microglial activation in a mouse model of α-synuclein overexpression

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This chapter examines microglial activation in a mouse model of α-synuclein overexpression. The chapter reviews evidence supporting a role for SYN, microglia, proinflammatory molecules, and the attendant oxidative stress in PD focusing on early proinflamatory events in a transgenic mouse model of PD with tyrosine hydroxylase promoter-directed overexpression of human α-synuclein (SYN WT +/+). The studies demonstrate that the SYN WT +/+ mice represent a novel model to further dissect important pathogenic epochs of disease with regard to microglial activation. The finding that microglia are activated at 1 month of age suggests that early anti-inflammatory intervention may preclude later pathology. The in vitro work demonstrating a direct effect of SYN on microglia advocates for prevention of SYN release. The observation that CD36 is involved in SYN-directed microglial activation portends the usefulness for small molecule inhibitors of CD36 as anti-inflammatory agents in this model. The studies confirm that SYN WT+/+ mice represents an important model for testing novel therapeutic agents to prevent aberrant microglial activation and for dissecting critical stages of disease progression.

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