jhnycmltly
2013-12-18 23:24:52 UTC
Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.
Neurobiol Aging. 2013 Nov 13.
Huang XT1, Qian ZM2, He X3, Gong Q3, Wu KC3, Jiang LR4, Lu LN3, Zhu ZJ3, Zhang HY5, Yung WH3, Ke Y6.
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
2Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, China. Electronic address: ***@fudan.edu.cn.
3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
4Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, China.
5State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
6School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. Electronic address: ***@cuhk.edu.hk.
Abstract
Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States.
In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties.
However, the relevant mechanism is unknown.
Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation.
HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice.
Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice.
However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet.
In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease.
Copyright © 2013 Elsevier Inc. All rights reserved.
KEYWORDS: Alzheimer's disease, Brain iron, Double transgenic APPswe/PS1dE9 mice (APP/PS mice), Huperzine A, The neuronal amyloid precursor protein (APP), Transferrin receptor 1
pii: S0197-4580(13)00572-1. doi: 10.1016/j.neurobiolaging.2013.11.004.
PMID:24332448
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
Neurobiol Aging. 2013 Nov 13.
Huang XT1, Qian ZM2, He X3, Gong Q3, Wu KC3, Jiang LR4, Lu LN3, Zhu ZJ3, Zhang HY5, Yung WH3, Ke Y6.
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
2Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, China. Electronic address: ***@fudan.edu.cn.
3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
4Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, China.
5State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
6School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. Electronic address: ***@cuhk.edu.hk.
Abstract
Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States.
In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties.
However, the relevant mechanism is unknown.
Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation.
HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice.
Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice.
However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet.
In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease.
Copyright © 2013 Elsevier Inc. All rights reserved.
KEYWORDS: Alzheimer's disease, Brain iron, Double transgenic APPswe/PS1dE9 mice (APP/PS mice), Huperzine A, The neuronal amyloid precursor protein (APP), Transferrin receptor 1
pii: S0197-4580(13)00572-1. doi: 10.1016/j.neurobiolaging.2013.11.004.
PMID:24332448
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk