Androgens modulate β-amyloid levels in male rat brain
作者： M. Ramsden , A. C. Nyborg , M. P. Murphy , L. Chang , F. Z. Stanczyk
DOI: 10.1046/J.1471-4159.2003.02114.X
关键词:
摘要: As a normal consequence of aging, men experience significant decline in androgen levels. Although the neural consequences age-related depletion remain unclear, recent evidence suggests link between low levels and development Alzheimer's disease (AD). Here, we test hypothesis that androgens act as endogenous modulators beta-amyloid protein (Abeta) To investigate this possibility, brain plasma Abeta were measured male rats with varying hormonal conditions. Depletion sex steroid hormones via gonadectomy (GDX) resulted increased comparison to gonadally intact rats. This GDX-induced increase was reversed by DHT supplementation, demonstrating functional role for modulating Abeta. These findings suggest may result accumulation thereby risk factor AD.
sci-hub.se 参考文章(25)
Howard N. Hodis, Frank Z. Stanczyk, Donna Shoupe, Robert Boostanfar, Wendy J. Mack, Richard J. Paulson, Cristin C. Slater, Chunying Zhang, Comparison of estrogen and androgen levels after oral estrogen replacement therapy. Journal of Reproductive Medicine. ,vol. 46, pp. 1052- 1056 ,(2001)
A.B. Jaffe, C.D. Toran-Allerand, P. Greengard, S.E. Gandy, Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. Journal of Biological Chemistry. ,vol. 269, pp. 13065- 13068 ,(1994) , 10.1016/S0021-9258(17)36796-0
Angelo Poletti, Luciano Martini, Androgen-activating enzymes in the central nervous systemProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998. The Journal of Steroid Biochemistry and Molecular Biology. ,vol. 69, pp. 117- 122 ,(1999) , 10.1016/S0960-0760(98)00150-2
Sam Gandy, Chemical andropause and amyloid-beta peptide. JAMA. ,vol. 285, pp. 2195- 2196 ,(2001) , 10.1001/JAMA.285.17.2195-A
Jeffrey P. Greenfield, Lawrence W. Leung, Dongming Cai, Krista Kaasik, Rachel S. Gross, Enrique Rodriguez-Boulan, Paul Greengard, Huaxi Xu, Estrogen Lowers Alzheimer β-Amyloid Generation by Stimulating trans-Golgi Network Vesicle Biogenesis * Journal of Biological Chemistry. ,vol. 277, pp. 12128- 12136 ,(2002) , 10.1074/JBC.M110009200
N Suzuki, T. Cheung, X. Cai, A Odaka, L Otvos, C Eckman, T. Golde, S. Younkin, An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants Science. ,vol. 264, pp. 1336- 1340 ,(1994) , 10.1126/SCIENCE.8191290
S. C. Papasozomenos, A. Shanavas, Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3β but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of τ: Implications for Alzheimer's disease Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 1140- 1145 ,(2002) , 10.1073/PNAS.032646799
Huaxi Xu, Gunnar K. Gouras, Jeffrey P. Greenfield, Bruno Vincent, Jan Naslund, Louis Mazzarelli, Gabriel Fried, Jasmina N. Jovanovic, Mary Seeger, Norman R. Relkin, Fang Liao, Frédéric Checler, Joseph D. Buxbaum, Brian T. Chait, Gopal Thinakaran, Sangram S. Sisodia, Rong Wang, Paul Greengard, Sam Gandy, Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nature Medicine. ,vol. 4, pp. 447- 451 ,(1998) , 10.1038/NM0498-447
E. Carro, J.L. Trejo, T. Gomez-Isla, D. LeRoith, I. Torres-Aleman, Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nature Medicine. ,vol. 8, pp. 1390- 1397 ,(2002) , 10.1038/NM1202-793
H. Zheng, H. Xu, S. N. Uljon, R. Gross, K. Hardy, J. Gaynor, J. Lafrancois, J. Simpkins, L. M. Refolo, S. Petanceska, R. Wang, K. Duff, Modulation of A(beta) peptides by estrogen in mouse models. Journal of Neurochemistry. ,vol. 80, pp. 191- 196 ,(2002) , 10.1046/J.0022-3042.2001.00690.X