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Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aβ Generation and Degradation in Neuroblastoma Cells.
J Nutr Health Aging 2015; 19(6):646-56JN

Abstract

OBJECTIVES

The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because of the elevated lipid peroxidation and increased reactive oxidative species in Alzheimer's disease (AD) many attempts have been made to slow down the progression of AD by utilizing the antioxidative action of vitamin E. Beside the mixed results of these studies nothing is known about the impact of vitamin E on the mechanisms leading to amyloid-β production and degradation being responsible for the plaque formation, one of the characteristic pathological hallmarks in AD. Here we systematically investigate the influence of different tocopherols on Aβ production and degradation in neuronal cell lines.

MEASUREMENTS

Beside amyloid-β level the mechanisms leading to Aβ production and degradation are examined.

RESULTS

Surprisingly, all tocopherols have shown to increase Aβ level by enhancing the Aβ production and decreasing the Aβ degradation. Aβ production is enhanced by an elevated activity of the involved enzymes, the β- and γ-secretase. These secretases are not directly affected, but tocopherols increase their protein level and expression. We could identify significant differences between the single tocopherols; whereas α-tocopherol had only minor effects on Aβ production, δ-tocopherol showed the highest potency to increase Aβ generation. Beside Aβ production, Aβ clearance was decreased by affecting IDE, one of the major Aβ degrading enzymes.

CONCLUSIONS

Our results suggest that beside the beneficial antioxidative effects of vitamin E, tocopherol has in respect to AD also a potency to increase the amyloid-β level, which differ for the analysed tocopherols. We therefore recommend that further studies are needed to clarify the potential role of these various vitamin E species in respect to AD and to identify the form which comprises an antioxidative property without having an amyloidogenic potential.

Authors+Show Affiliations

Marcus Grimm, Kirrberger Str.1, Building 90.1, 66421 Homburg/Saar, Germany; Tel: +49-6841-1647919; Fax: +49-6841-1624137; E-mail: Marcus.Grimm@uks.eu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26054501

Citation

Grimm, M O W., et al. "Vitamin E: Curse or Benefit in Alzheimer's Disease? a Systematic Investigation of the Impact of Α-, Γ- and δ-Tocopherol On Aβ Generation and Degradation in Neuroblastoma Cells." The Journal of Nutrition, Health & Aging, vol. 19, no. 6, 2015, pp. 646-56.
Grimm MO, Stahlmann CP, Mett J, et al. Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aβ Generation and Degradation in Neuroblastoma Cells. J Nutr Health Aging. 2015;19(6):646-56.
Grimm, M. O., Stahlmann, C. P., Mett, J., Haupenthal, V. J., Zimmer, V. C., Lehmann, J., ... Hartmann, T. (2015). Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aβ Generation and Degradation in Neuroblastoma Cells. The Journal of Nutrition, Health & Aging, 19(6), pp. 646-56. doi:10.1007/s12603-015-0506-z.
Grimm MO, et al. Vitamin E: Curse or Benefit in Alzheimer's Disease? a Systematic Investigation of the Impact of Α-, Γ- and δ-Tocopherol On Aβ Generation and Degradation in Neuroblastoma Cells. J Nutr Health Aging. 2015;19(6):646-56. PubMed PMID: 26054501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aβ Generation and Degradation in Neuroblastoma Cells. AU - Grimm,M O W, AU - Stahlmann,C P, AU - Mett,J, AU - Haupenthal,V J, AU - Zimmer,V C, AU - Lehmann,J, AU - Hundsdörfer,B, AU - Endres,K, AU - Grimm,H S, AU - Hartmann,T, PY - 2015/6/10/entrez PY - 2015/6/10/pubmed PY - 2016/6/10/medline SP - 646 EP - 56 JF - The journal of nutrition, health & aging JO - J Nutr Health Aging VL - 19 IS - 6 N2 - OBJECTIVES: The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because of the elevated lipid peroxidation and increased reactive oxidative species in Alzheimer's disease (AD) many attempts have been made to slow down the progression of AD by utilizing the antioxidative action of vitamin E. Beside the mixed results of these studies nothing is known about the impact of vitamin E on the mechanisms leading to amyloid-β production and degradation being responsible for the plaque formation, one of the characteristic pathological hallmarks in AD. Here we systematically investigate the influence of different tocopherols on Aβ production and degradation in neuronal cell lines. MEASUREMENTS: Beside amyloid-β level the mechanisms leading to Aβ production and degradation are examined. RESULTS: Surprisingly, all tocopherols have shown to increase Aβ level by enhancing the Aβ production and decreasing the Aβ degradation. Aβ production is enhanced by an elevated activity of the involved enzymes, the β- and γ-secretase. These secretases are not directly affected, but tocopherols increase their protein level and expression. We could identify significant differences between the single tocopherols; whereas α-tocopherol had only minor effects on Aβ production, δ-tocopherol showed the highest potency to increase Aβ generation. Beside Aβ production, Aβ clearance was decreased by affecting IDE, one of the major Aβ degrading enzymes. CONCLUSIONS: Our results suggest that beside the beneficial antioxidative effects of vitamin E, tocopherol has in respect to AD also a potency to increase the amyloid-β level, which differ for the analysed tocopherols. We therefore recommend that further studies are needed to clarify the potential role of these various vitamin E species in respect to AD and to identify the form which comprises an antioxidative property without having an amyloidogenic potential. SN - 1760-4788 UR - https://www.unboundmedicine.com/medline/citation/26054501/Vitamin_E:_Curse_or_Benefit_in_Alzheimer's_Disease_A_Systematic_Investigation_of_the_Impact_of_α__γ__and_δ_Tocopherol_on_Aβ_Generation_and_Degradation_in_Neuroblastoma_Cells_ L2 - http://www.diseaseinfosearch.org/result/5160 DB - PRIME DP - Unbound Medicine ER -