Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity

Figueiredo, Claudia P., Bicca, Maria A., Latini, Alexandra, Prediger, Rui Daniel S., Medeiros, Rodrigo and Calixto, Joao B. (2011) Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity. Journal of Alzheimers Disease, 24 1: 61-75. doi:10.3233/JAD-2010-101320


Author Figueiredo, Claudia P.
Bicca, Maria A.
Latini, Alexandra
Prediger, Rui Daniel S.
Medeiros, Rodrigo
Calixto, Joao B.
Title Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity
Journal name Journal of Alzheimers Disease   Check publisher's open access policy
ISSN 1387-2877
1875-8908
Publication date 2011-06-01
Sub-type Article (original research)
DOI 10.3233/JAD-2010-101320
Open Access Status Not yet assessed
Volume 24
Issue 1
Start page 61
End page 75
Total pages 15
Place of publication Amsterdam, Netherlands
Publisher I O S Press
Language eng
Formatted 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 Aβ 1-40-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 Aβ 1-40 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 Aβ 1-40. 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 Aβ 1-40 peptide.
Keyword Alpha-tocopherol
Amyloid-β
Cognition
Folic acid
Mitochondrial complexes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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