Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease

摘要: During the past three decades, Wingless-type MMTV integration site (Wnt) signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence points to a dysregulation of Wnt major neurodegenerative pathologies including Parkinson's disease (PD), common disorder characterized by progressive loss midbrain dopaminergic (mDA) neurons deregulated activation astrocytes microglia. This review highlights emerging link between key inflammatory pathways during mDA neuron damage/repair PD progression. In particular, we summarize recent documenting that aging neurotoxicant exposure strongly antagonize Wnt/β-catenin subventricular zone (SVZ) neuroprogenitors via astrocyte-microglial interactions. Dysregulation crosstalk anti-oxidant/anti-inflammatory delineate novel mechanisms driving decline SVZ plasticity with age limited nigrostriatal self-repair PD. These findings hold promise therapies target enhance endogenous restoration neuronal outcome age-dependent diseases, such