کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4331154 1614295 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nrf2-mediated protection against 6-hydroxydopamine
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Nrf2-mediated protection against 6-hydroxydopamine
چکیده انگلیسی

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by cell loss in the substantia nigra resulting in striatal dopamine depletion. Although the cause of sporadic PD is unknown, oxidative stress is thought to contribute to disease pathogenesis. One mechanism by which cells defend themselves against oxidative stress is through the transcriptional upregulation of cytoprotective genes. Under oxidative stress conditions, the transcription factor NF-E2-related factor (Nrf2) binds to the antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. Here we show that loss of Nrf2-mediated transcription exacerbates vulnerability to the neurotoxin 6-hydroxydopamine (6-OHDA) both in vitro and in vivo. We further demonstrate that activation of the Nrf2-ARE pathway by the known chemical inducer tert-butylhydroquinone can protect against 6-OHDA in vitro. Induction of this pathway by transplantation of astrocytes overexpressing Nrf2 can protect against 6-OHDA-induced damage in the living mouse. This suggests that the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing cell death in PD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1144, 4 May 2007, Pages 192–201
نویسندگان
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