多巴胺能
黑质
氧化应激
小胶质细胞
帕金森病
药理学
下调和上调
激活剂(遗传学)
化学
生物
多巴胺
神经科学
医学
生物化学
免疫学
内科学
炎症
疾病
基因
作者
Yuta Masaki,Yasuhiko Izumi,Akitaka Matsumura,Akinori Akaike,Toshiaki Kume
标识
DOI:10.1016/j.ejphar.2017.02.005
摘要
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN), and oxidative stress is thought to contribute to the pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which is a cellular defense system against oxidative stress, is a promising target for therapeutics aimed at reducing neuronal death in PD. Previously, we have isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla leaves as an activator of the Nrf2-ARE pathway. The present study showed the protective effect of DDC on PD models in vivo and in vitro. In a 6-hydroxydopamine (6-OHDA)-induced hemiparkinson's disease mouse model, intracerebral administration of DDC suppressed the dopaminergic neuronal loss and behavioral dysfunction. DDC upregulated the expression of heme oxygenase-1 (HO-1), one of the ARE-driven antioxidant enzymes, in astrocytes and microglia of the SN. In primary mesencephalic cultures, treatment with DDC also increased the HO-1 expression in astrocytes and microglia. DDC showed a protective effect against 6-OHDA-induced dopaminergic neuronal death, and the effect was suppressed by an HO-1 inhibitor. These results suggest that DDC prevents dopaminergic neurons from oxidative stress by upregulation of glial expression of HO-1.
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