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Article type: Research Article
Authors: Hagl, Stephaniea | Grewal, Rekhaa | Ciobanu, Iona | Helal, Amrb | Khayyal, Mohamed T.c | Muller, Walter E.a | Eckert, Gunter P.a; *
Affiliations: [a] Department of Pharmacology, Campus Riedberg, Goethe-University, Frankfurt, Germany | [b] IT&M, Giza, Egypt | [c] Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
Correspondence: [*] Correspondence to: Gunter P. Eckert, PhD, Goethe-University, Department of Pharmacology, Biocenter, N260 R1.09, Max-von-Laue Str. 9, 60438 Frankfurt, Germany. Tel.: +49 69 798 29 378; Fax: +49 69 798 29 374; E-mail: [email protected].
Abstract: Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17–27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD.
Keywords: Alzheimer's disease, bioenergetics, mitochondria, mitochondrial dynamics, nitrosative stress, nutrition, PC12 cells, respiration, rice bran extract
DOI: 10.3233/JAD-132084
Journal: Journal of Alzheimer's Disease, vol. 43, no. 3, pp. 927-938, 2015
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