Title: | Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease |
Authors: | Omori, Chiori Browse this author |
Motodate, Rika Browse this author |
Shiraki, Yuzuha Browse this author |
Chiba, Kyoko Browse this author |
Sobu, Yuriko Browse this author |
Kimura, Ayano Browse this author |
Nakaya, Tadashi Browse this author →KAKEN DB |
Kondo, Hikaru Browse this author |
Kurumiya, Satoshi Browse this author |
Tanaka, Toru Browse this author |
Yamamoto, Kazuo Browse this author |
Nakajima, Motowo Browse this author |
Suzuki, Toshiharu Browse this author →KAKEN DB |
Hata, Saori Browse this author →KAKEN DB |
Keywords: | 5-Aminolevulinic acid |
Cytochrome c oxidase |
Aging |
Alzheimer's disease |
Amyloid-β |
Synaptotagmin |
Issue Date: | 22-Jun-2016 |
Publisher: | Taylor & Francis |
Journal Title: | Nutritional neuroscience |
Volume: | 20 |
Issue: | 9 |
Start Page: | 538 |
End Page: | 546 |
Publisher DOI: | 10.1080/1028415X.2016.1199114 |
PMID: | 27329428 |
Abstract: | The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity of cytochrome c oxidase (COX/complex IV) decreases in patients with Alzheimer's disease (AD). COX, a mitochondrial inner membrane protein complex that contains heme, plays an essential role in the electron transport chain that generates ATP. Heme synthesis begins with 5-aminolevulinic acid (5-ALA) in mitochondria. 5-ALA synthetase is the rate-limiting enzyme in heme synthesis, suggesting that supplementation with 5-ALA might help preserve mitochondrial activity in the aged brain. We administered a diet containing 5-ALA to triple-transgenic AD (3xTg-AD) model mice for 6 months, starting at 3 months of age. COX activity and protein expression, as well as mitochondrial membrane potential, were significantly higher in brains of 5-ALA-fed mice than in controls. Synaptotagmin protein levels were also significantly higher in 5-ALA-fed mice, suggesting improved preservation of synapses. Although brain A levels tended to decrease in 5-ALA-fed mice, we observed no other significant changes in other biochemical and pathological hallmarks of AD. Nevertheless, our study suggests that daily oral administration of 5-ALA could preserve mitochondrial enzyme activities in the brains of aged individuals, thereby contributing to the preservation of neural activity. |
Rights: | This is an Accepted Manuscript of an article published by Taylor & Francis in Nutr. Neurosci. on 22 Jun 2016, available online: http://www.tandfonline.com/10.1080/1028415X.2016.1199114. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/67709 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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