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Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease

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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
Alzheimer's disease
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:
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 羽田 沙緒里

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