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Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2011; Vol. 24 (1), pp. 61-75. - Publication Year :
- 2011
-
Abstract
- Early symptoms of Alzheimer's disease (AD) have been attributed to amyloid-β (Aβ) toxicity. The pathophysiology of AD is complex and involves several different biochemical pathways, including defective Aβ protein metabolism, neuroinflammation, oxidative processes, and mitochondrial dysfunction. In the current study, we assessed the molecular mechanisms, mainly the modifications in the activity of mitochondrial complexes, whereby the association of folic acid and α-tocopherol protects mice against the Aβ-induced neurotoxicity. Oral treatment with folic acid (50 mg/kg) plus α-tocopherol (500 mg/kg), once a day during 14 consecutive days, protected mice against the Aβ₁₋₄₀-induced cognitive decline, synaptic loss, and neuronal death. However, chronic treatment comprising folic acid plus α-tocopherol was ineffective on Aβ-induced glial cell activation, suggesting that the effect of this treatment is independent of anti-inflammatory features. Interestingly, the results obtained in our study suggest that mitochondrial energy metabolism is impaired by the Aβ peptide, and upregulation of mitochondrial genes may be a compensatory response, as demonstrated by the increase in mitochondrial complexes I, II, and IV activity, in the hippocampus of mice, after Aβ₁₋₄₀ injection. Of note, the chronic treatment comprising folic acid plus α-tocopherol prevented the increase in the activity of mitochondrial complexes I and IV induced by Aβ₁₋₄₀. Together, these results show the antioxidant effect of the combination of folic acid and α-tocopherol, as observed by the decrease in NO generation from iNOS and nNOS, preventing an increase in the activity of mitochondrial complexes, mainly I and IV, and the neuronal death induced by the Aβ₁₋₄₀ peptide.
- Subjects :
- Amyloid beta-Peptides antagonists & inhibitors
Animals
Antioxidants administration & dosage
Drug Therapy, Combination
Electron Transport drug effects
Electron Transport physiology
Electron Transport Complex I metabolism
Electron Transport Complex II metabolism
Electron Transport Complex IV metabolism
Enzyme Activation drug effects
Enzyme Activation physiology
Humans
Male
Mice
Mitochondria drug effects
Peptide Fragments antagonists & inhibitors
Amyloid beta-Peptides toxicity
Folic Acid administration & dosage
Mitochondria metabolism
Multienzyme Complexes metabolism
Peptide Fragments toxicity
alpha-Tocopherol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 21157027
- Full Text :
- https://doi.org/10.3233/JAD-2010-101320