Fk506&reduces&neuroinflammation&and&dopaminergic& Neurodegeneration&in&an&α8synuclein8based&rat&model&for& Parkinson's&disease.% Fk506 Reduces Neuroinflammation and Dopaminergic Neurodegeneration in an - Synuclein-based Rat Model for Parkinson's Disease Authors

Alpha-synuclein (-synuclein) is considered a key player in Parkinson's disease (PD), but the exact relationship between-synuclein aggregation and dopaminergic (DA) neurodegeneration remains unresolved. There is increasing evidence that neuroinflammatory processes are closely linked to DA 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-synuclein overexpression rat model. Treatment with FK506 significantly increased the survival of dopaminergic neurons in a dose-dependent manner. No reduction in-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/ macrophages. These data suggest that the anti-inflammatory properties of FK506 decrease neurodegeneration in this-synuclein-based PD model, pointing to a causal role of neuroinflammation in the pathogenesis of PD.