Protective effects of Nrf2–ARE activator on dopaminergic neuronal loss in Parkinson disease model mice: Possible involvement of heme oxygenase-1
| Autor: | Yasuhiko Izumi, Akinori Akaike, Yuri Inose, Yuki Takada-Takatori, Yutaka Koyama, Shuji Kaneko, Toshiaki Kume |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
NF-E2-Related Factor 2 Substantia nigra Pharmacology medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Parkinson Disease Secondary Oxidopamine Cell Death Chemistry Activator (genetics) Dopaminergic Neurons General Neuroscience Dopaminergic Neurodegeneration medicine.disease Antioxidant Response Elements Corpus Striatum Up-Regulation Substantia Nigra Heme oxygenase Oxidative Stress 030104 developmental biology Signal transduction Heme Oxygenase-1 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Neuroscience Letters. 736:135268 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2020.135268 |
| Popis: | Parkinson disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra, and oxidative stress is thought to contribute to this pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is thereby a potential target for therapeutics to reduce neurodegeneration in PD. Previously, we identified TPNA10168 from a chemical library as an activator of the Nrf2-ARE pathway, and the present study examined the effects of TPNA10168 on an in vivo PD model. Subcutaneous administration of TPNA10168 was associated with inhibited dopaminergic neuronal loss and behavioral impairment in 6-hydroxydopamine-induced PD model mice. Heme oxygenase-1 (HO-1) is an antioxidant enzyme expressed downstream of the Nrf2-ARE signaling pathway, and we observed that HO-1 protein levels were upregulated by TPNA10168 in the mouse brain. These results suggest that TPNA10168 inhibits dopaminergic neuronal death in PD model mice, and that upregulation of HO-1 might participate in this effect. |
| Databáze: | OpenAIRE |
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