Beneficial effects of melatonin in experimental models of Alzheimer disease

被引:56
作者
Cheng, Y
Feng, Z
Zhang, QZ
Zhang, JT [1 ]
机构
[1] Chinese Acad Med Sci, Inst Mat Med, Dept Pharmacol, Beijing 100050, Peoples R China
[2] Peking Union Med Coll, Beijing 100050, Peoples R China
[3] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92161 USA
[4] Vet Affairs Med Ctr, La Jolla, CA 92161 USA
[5] Shandong Univ, Coll Pharm, Dept Pharmacol, Jinan 250012, Peoples R China
关键词
melatonin; Alzheimer disease; beta-amyloid protein; calcium overload; APP transgenic mice; ovariectomized rats; tau protein hyperphosphorylation;
D O I
10.1111/j.1745-7254.2006.00267.x
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxidant and free radical scavenger. Additionally, melatonin stimulates several antioxidative enzymes and improves mitochondrial energy metabolism. These findings led us to study amyloid precursor protein transgenic mice, ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe whether melatonin had any effect on Alzheimer's symptoms or pathological changes. We found that melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of beta-amyloid (A beta) deposition and A beta fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation. These actions may potentially slow down or stop the progression of dementia.
引用
收藏
页码:129 / 139
页数:11
相关论文
共 94 条
[1]   Melatonin, mitochondria, and cellular bioenergetics [J].
Acuña-Castroviejo, D ;
Martín, M ;
Macías, M ;
Escames, G ;
León, J ;
Khaldy, H ;
Reiter, RJ .
JOURNAL OF PINEAL RESEARCH, 2001, 30 (02) :65-74
[2]   The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease [J].
Aisen, PS .
LANCET NEUROLOGY, 2002, 1 (05) :279-284
[3]   Mitochondria, free radicals, and neurodegeneration [J].
Beal, MF .
CURRENT OPINION IN NEUROBIOLOGY, 1996, 6 (05) :661-666
[4]   Role of protein phosphatase-2A and-1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain [J].
Bennecib, M ;
Gong, CX ;
Grundke-Iqbal, I ;
Iqbal, K .
FEBS LETTERS, 2000, 485 (01) :87-93
[5]   Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer's [J].
Bhavnani, BR .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2003, 85 (2-5) :473-482
[6]   The neurochemistry of Alzheimer's disease [J].
Blennow, K ;
Cowburn, RF .
ACTA NEUROLOGICA SCANDINAVICA, 1996, 94 :77-86
[7]   Acetylcholinesterase-positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein London mutant transgenic mice [J].
Bronfman, FC ;
Moechars, D ;
Van Leuven, F .
NEUROBIOLOGY OF DISEASE, 2000, 7 (03) :152-168
[8]  
Butterfield DA, 2002, NEUROBIOL AGING, V23, P655
[9]   Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy [J].
Cagnacci, A ;
Arangino, S ;
Angiolucci, M ;
Melis, GB ;
Tarquini, R ;
Renzi, A ;
Volpe, A .
JOURNAL OF PINEAL RESEARCH, 2000, 29 (03) :152-158
[10]  
Chan SL, 1999, J NEUROSCI RES, V57, P315, DOI 10.1002/(SICI)1097-4547(19990801)57:3<315::AID-JNR3>3.3.CO