Journal article

Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes

Jeffrey R Liddell, Sarka Lehtonen, Clare Duncan, Velta Keksa-Goldsteine, Anna-Liisa Levonen, Gundars Goldsteins, Tarja Malm, Anthony R White, Jari Koistinaho, Katja M Kanninen



BACKGROUND: Endogenous defense against oxidative stress is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2). The normal compensatory mechanisms to combat oxidative stress appear to be insufficient to protect against the prolonged exposure to reactive oxygen species during disease. Counterbalancing the effects of oxidative stress by up-regulation of Nrf2 signaling has been shown to be effective in various disease models where oxidative stress is implicated, including Alzheimer's disease. Stimulation of Nrf2 signaling by small-molecule activators is an appealing strategy to up-regulate the endogenous defense mechanisms of cells. METHODS: Here, we investigate Nrf2 induction by t..

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Funding Acknowledgements

We gratefully acknowledge Prof. Masayuki Yamamoto (Tohoku University) for the provision of Nrf2-deficient mice and thank Ms. Laila Kaskela, Ms. Mirka Tikkanen, Ms. Sara Wojciechowski, Ms. Riitta Kauppinen, and Ms. Raisa Giniatullina for technical assistance. This study was supported by The Sigrid Juselius Foundation, The Academy of Finland, and The Finnish Cultural Foundation. JRL is supported by a National Health and Medical Research Council Peter Doherty Fellowship. The funding sources had no role in the study design, data collection and analysis, preparation of the manuscript, or decision to publish.