Nuclear Factor Erythroid 2
Nuclear factor erythroid 2-related factor 2 protects against beta amyloid
Katja Kanninen a,c, Tarja M. Malm a,c, Henna-Kaisa Jyrkkänen b,c, Gundars Goldsteins a,c,
Velta Keksa-Goldsteine a,c, Heikki Tanila a,c, Masayuki Yamamoto e,f, Seppo Ylä-Herttuala b,c,
Anna-Liisa Levonen b,c, Jari Koistinaho a,c,d
a Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, 70211 Kuopio, Finland
b Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, 70211 Kuopio, Finland
c Biocenter Kuopio, Kuopio University, P.O. Box 1627, 70211 Kuopio, Finland
d Department of Oncology, Kuopio University Hospital, P.O. Box 1627, 70211 Kuopio, Finland
e Center for TARA and JST-ERATO Environmental Response Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan
f Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). In the pathogenesis of Alzheimer’s disease (AD) current evidence supports the role of oxidative stress. Considering the protective role of Nrf2 against oxidative injury, we studied Nrf2 and Nrf2-ARE target genes in transgenic AD mice and tested whether Nrf2 could confer neuroprotection against amyloid-beta peptides (Aβ). Nrf2-ARE pathway was attenuated in APP/PS1 transgenic mouse brain at the time of Aβ deposition. Boosting the activity of the Nrf2-ARE pathway by tert-butylhydroquinone treatment or adenoviral Nrf2 gene transfer protected against Aβ toxicity. This neuroprotection was associated with increased expression of Nrf2 target genes and reduced phosphorylation of p66Shc, a marker of increased susceptibility for oxidative stress. The findings suggest that the Nrf2-ARE pathway may be impaired in Alzheimer’s disease and that induction of the Nrf2-ARE defense mechanism may prevent or delay Alzheimer’s-like pathology.
Note from ISS: NrF2 is activated by sulforaphane. Crucifer sprouts such as broccoli, radish and kale sprouts are the most potent natural sources of sulforaphane. Crucifer sprouts often produce10 to 100 times the amount of sulforaphane as their corresponding mature vegetables. And mature crucifers, such as broccoli are usually consumed after cooking. Cooking destroys over 90% of sulforaphane’s bioactivity.