title: Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer's Disease.
abstract: One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD.
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. marcus.grimm@uks.eu.|Neurodegeneration and Neurobiology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. marcus.grimm@uks.eu.|Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. marcus.grimm@uks.eu.
authors: Marcus O W
authors: MO
authors: Grimm
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. liesa.regner@uks.eu.
authors: Liesa
authors: L
authors: Regner
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. janine.mett@uks.eu.
authors: Janine
authors: J
authors: Mett
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. christoph.stahlmann@uks.eu.
authors: Christoph P
authors: CP
authors: Stahlmann
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. pascals91@gmail.com.|Institute of Bioanalytical Chemistry, Saarland University, 66123 Saarbrücken, Germany. pascals91@gmail.com.
authors: Pascal
authors: P
authors: Schorr
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. christophernelke@yahoo.de.
authors: Christopher
authors: C
authors: Nelke
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. olga.streidenberger@uks.eu.
authors: Olga
authors: O
authors: Streidenberger
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. hannah.stoetzel@uks.eu.
authors: Hannah
authors: H
authors: Stoetzel
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. Jakob.winkler@hotmail.de.
authors: Jakob
authors: J
authors: Winkler
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. shatharamadhan@yahoo.com.
authors: Shatha R
authors: SR
authors: Zaidan
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. andrea.thiel@uks.eu.
authors: Andrea
authors: A
authors: Thiel
authors: Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg-University Mainz, Untere Zahlbacher Straße 8, 55131 Mainz, Germany. Kristina.Endres@unimedizin-mainz.de.
authors: Kristina
authors: K
authors: Endres
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. heike.grimm@uks.eu.
authors: Heike S
authors: HS
authors: Grimm
authors: Institute of Bioanalytical Chemistry, Saarland University, 66123 Saarbrücken, Germany. dietrich.volmer@mx.uni-saarland.de.
authors: Dietrich A
authors: DA
authors: Volmer
authors: Experimental Neurology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. tobias.hartmann@mx.uni-saarland.de.|Neurodegeneration and Neurobiology, Saarland University, Kirrberger Straße 1, 66421 Homburg/Saar, Germany. tobias.hartmann@mx.uni-saarland.de.|Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg-University Mainz, Untere Zahlbacher Straße 8, 55131 Mainz, Germany. tobias.hartmann@mx.uni-saarland.de.
authors: Tobias
authors: T
authors: Hartmann
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000975:Antioxidants / Q000008:administration & dosage; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D024508:Tocotrienols / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D024508:Tocotrienols; D014810:Vitamin E; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer´s disease; Aβ degradation; amyloid-β; tocopherol; tocotrienol; vitamin E; β-secretase; γ-secretase