Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic str...Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum （ER） stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti- oxidative stress properties and protects against DA neu- ronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine （6-OHDA）- induced cytotoxicity by attenuating ER stress. Further- more, treatment of a DA neuronal cell line （SN4741） and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results sug- gest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.展开更多
基金supported by the National Basic Research Development Program(973 Program)of China(2011CB510000)the National Natural Science Foundation of China(31371400)
文摘Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum （ER） stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti- oxidative stress properties and protects against DA neu- ronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine （6-OHDA）- induced cytotoxicity by attenuating ER stress. Further- more, treatment of a DA neuronal cell line （SN4741） and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results sug- gest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.
