Abstract |
Huperzine A (HupA) is a kind of Lycopodium alkaloid with potential disease-modifying qualities that has been reported to protect against β- amyloid (Aβ)-mediated mitochondrial damage in Alzheimer's disease. However, the fundamental molecular mechanism underlying the protective action of HupA against Aβ-mediated mitochondrial malfunction is not completely understood. Recently, the mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD) protein has been reported to facilitate Aβ-induced mitochondrial damage, resulting in mitochondrial malfunction and cell death. Our study found that HupA, but not the acetylcholinesterase inhibitor tacrine, reduced the deposition of Aβ and the ABAD level, and further reduced Aβ-ABAD complexes, thereby improving cerebral mitochondrial function in APP/PS1 mice. This was accompanied by attenuated reactive oxygen species overload, as well as increases adenosine triphosphate levels. Moreover, HupA decreased the release of cytochrome-c from mitochondria and the level of cleaved caspase-3, thereby increasing dissociated brain cell viability in APP/PS1 mice. Thus, our study demonstrated that a reduction in ABAD was involved in the protective mechanism of HupA on the cerebral mitochondrial function in APP/PS1 mice.
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Authors | Xiaodan Xiao, Qingzhuang Chen, Xinhong Zhu, Yong Wang |
Journal | Neurobiology of aging
(Neurobiol Aging)
Vol. 81
Pg. 77-87
(09 2019)
ISSN: 1558-1497 [Electronic] United States |
PMID | 31252207
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier Inc. All rights reserved. |
Chemical References |
- Alkaloids
- Amyloid beta-Peptides
- Neuroprotective Agents
- Reactive Oxygen Species
- Sesquiterpenes
- huperzine A
- Tacrine
- Cytochromes c
- 3-Hydroxyacyl CoA Dehydrogenases
- Hsd17b10 protein, mouse
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Topics |
- 3-Hydroxyacyl CoA Dehydrogenases
(metabolism)
- Alkaloids
(pharmacology, therapeutic use)
- Alzheimer Disease
(drug therapy, metabolism)
- Amyloid beta-Peptides
(adverse effects, metabolism)
- Animals
- Brain
(cytology, metabolism)
- Cell Survival
(drug effects)
- Cytochromes c
(metabolism)
- Disease Models, Animal
- Male
- Mice, Transgenic
- Mitochondria
(metabolism)
- Neuroprotective Agents
(pharmacology, therapeutic use)
- Reactive Oxygen Species
(metabolism)
- Sesquiterpenes
(pharmacology, therapeutic use)
- Tacrine
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