FK506 reduces neuroinflammation and dopaminergic neurodegeneration in an α-synuclein-based rat model for Parkinson's disease.
Creators
- 1. KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Flanders, Belgium
- 2. KU Leuven, Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Flanders, Belgium
- 3. Leuven University Hospital and KU Leuven, Division of Nephrology and Renal Transplantation, Department of Microbiology and Immunology, Leuven, Belgium.
- 4. KU Leuven, Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Flanders, Belgium and KU Leuven, Leuven Viral Vector Core, Leuven, Belgium
- 5. KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Flanders, Belgium and KU Leuven, Leuven Viral Vector Core, Leuven, Belgium
Description
Alpha-synuclein (α-synuclein) is considered a key player in Parkinson's disease (PD), but the exact relationship between α-synuclein aggregation and dopaminergic neurodegeneration remains unresolved. There is increasing evidence that neuroinflammatory processes are closely linked to dopaminergic cell death, but whether the inflammatory process is causally involved in PD or rather reflects secondary consequences of nigrostriatal pathway injury is still under debate. We evaluated the therapeutic effect of the immunophilin ligand FK506 in a rAAV2/7 α-synuclein overexpression rat model. Treatment with FK506 significantly increased the survival of dopaminergic neurons in a dose-dependent manner. No reduction in α-synuclein aggregation was apparent in this time window, but FK506 significantly lowered the infiltration of both T helper and cytotoxic T cells and the number and subtype of microglia and macrophages. These data suggest that the anti-inflammatory properties of FK506 decrease neurodegeneration in this α-synuclein-based PD model, pointing to a causal role of neuroinflammation in the pathogenesis of PD.
Files
Van_der_Perren_NeurobiolAging_2015-P13b-AAM-FK506.pdf
Files
(1.3 MB)
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