During the past three decades, the Wingless-type MMTV integration site （Wnt） signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence po...During the past three decades, the 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 signaling in major neurodegenerative pathologies including Parkinson＇s disease （PD）, a common neurodegenerative disorder characterized by the pro- gressive loss of midbrain dopaminergic （mDA） neurons and deregulated activation of astrocytes and microglia. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/β-catenin signaling in mDA neurons and subventricular zone （SVZ） neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/β-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostriatal dopaminergic self-repair in PD. These findings hold a promise in devetoping therapies that target Wnt/β-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.展开更多
During the past three decades, Wingtess/Int （Wnt）signaling has emerged as an essential regu{ator crucial for neuronal development and maintenance （Inestrosa and Arenas, 201_0）. In addition, Wnt signal- ing was rec...During the past three decades, Wingtess/Int （Wnt）signaling has emerged as an essential regu{ator crucial for neuronal development and maintenance （Inestrosa and Arenas, 201_0）. In addition, Wnt signal- ing was recently shown to be involved in the regula- tion of synaptic function and plasticity, which is critical for learning and memory （Oliva et aL, 2013）. Deregulation of Wnt signaling has been proposed as a key contributor to the pathogenesis of neurode- generative disorders including Alzheimer＇s disease （AD） and Parkinson＇s disease （PD）. This increasing knowledge of the specific roles of Wnt signaling cascades during different stages of life has suggested innovative therapeutic strategies for the treatment of neurodegenerative diseases.展开更多
文摘During the past three decades, the 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 signaling in major neurodegenerative pathologies including Parkinson＇s disease （PD）, a common neurodegenerative disorder characterized by the pro- gressive loss of midbrain dopaminergic （mDA） neurons and deregulated activation of astrocytes and microglia. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/β-catenin signaling in mDA neurons and subventricular zone （SVZ） neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/β-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostriatal dopaminergic self-repair in PD. These findings hold a promise in devetoping therapies that target Wnt/β-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.
文摘During the past three decades, Wingtess/Int （Wnt）signaling has emerged as an essential regu{ator crucial for neuronal development and maintenance （Inestrosa and Arenas, 201_0）. In addition, Wnt signal- ing was recently shown to be involved in the regula- tion of synaptic function and plasticity, which is critical for learning and memory （Oliva et aL, 2013）. Deregulation of Wnt signaling has been proposed as a key contributor to the pathogenesis of neurode- generative disorders including Alzheimer＇s disease （AD） and Parkinson＇s disease （PD）. This increasing knowledge of the specific roles of Wnt signaling cascades during different stages of life has suggested innovative therapeutic strategies for the treatment of neurodegenerative diseases.
