N-acetyl serotonin derivatives as potent neuroprotectants for retinas
作者： J. Shen , K. Ghai , P. Sompol , X. Liu , X. Cao
关键词:
摘要: N-acetylserotonin (NAS) is synthesized from serotonin by arylalkylamine N-acetyltransferase (AANAT), which predominantly expressed in the pineal gland and retina. NAS activates TrkB a circadian manner exhibits antidepressant effects TrkB-dependent manner. It also enhances neurogenesis hippocampus sleep-deprived mice. Here we report identification of derivatives that possess much more robust neurotrophic with improved pharmacokinetic profiles. The compound N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) selectively receptor greater potency than NAS. potently protects retinas light-induced retinal degeneration (LIRD), tightly coupled pronounced activation retinas. Pharmacokinetic studies demonstrate this stable serum liver microsomes. can pass blood–brain barrier blood–retinal barrier. Hence, HIOC good lead for further drug development treating degenerative diseases.
harvard.edu
sci-hub.se 参考文章(42)
M Vidal-Sanz, P Peinado-Ramón, M Salvador, M P Villegas-Pérez, Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study Investigative Ophthalmology & Visual Science. ,vol. 37, pp. 489- 500 ,(1996)
Yoshihito Honda, Tohru Tatsuno, Hidenobu Tanihara, Chikao Nakayama, Hiroshi Noguchi, Kazuhito Ikeda, BDNF attenuates retinal cell death caused by chemically induced hypoxia in rats. Investigative Ophthalmology & Visual Science. ,vol. 40, pp. 2130- 2140 ,(1999)
Matthew M. LaVail, Michael T. Matthes, Douglas Yasumura, Kazuhiko Unoki, Roy H. Steinberg, Cathy Lau-Villacorta, Ching-Hwa Sung, Protection of mouse photoreceptors by survival factors in retinal degenerations. Investigative Ophthalmology & Visual Science. ,vol. 39, pp. 592- 602 ,(1998)
JE Johnson, YA Barde, M Schwab, H Thoenen, Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells The Journal of Neuroscience. ,vol. 6, pp. 3031- 3038 ,(1986) , 10.1523/JNEUROSCI.06-10-03031.1986
Yun-Tao Ma, Ted Hsieh, M. Elizabeth Forbes, James E. Johnson, Douglas O. Frost, BDNF Injected into the Superior Colliculus Reduces Developmental Retinal Ganglion Cell Death The Journal of Neuroscience. ,vol. 18, pp. 2097- 2107 ,(1998) , 10.1523/JNEUROSCI.18-06-02097.1998
G Carmignoto, L Maffei, P Candeo, R Canella, C Comelli, Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. The Journal of Neuroscience. ,vol. 9, pp. 1263- 1272 ,(1989) , 10.1523/JNEUROSCI.09-04-01263.1989
Solon Thanos, Mathias Bahr, Yves-Alain Barde, Jens Vanselow, Survival and Axonal Elongation of Adult Rat Retinal Ganglion Cells. European Journal of Neuroscience. ,vol. 1, pp. 19- 26 ,(1989) , 10.1111/J.1460-9568.1989.TB00770.X
Jörg Mey, Solon Thanos, Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo Brain Research. ,vol. 602, pp. 304- 317 ,(1993) , 10.1016/0006-8993(93)90695-J
Joseph F. Poduslo, Geoffrey L. Curran, Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF Molecular Brain Research. ,vol. 36, pp. 280- 286 ,(1996) , 10.1016/0169-328X(95)00250-V
Dougal J. Morton, Both hydroxy- and methoxyindoles modify basal temperature in the rat. Journal of Pineal Research. ,vol. 4, pp. 1- 5 ,(1987) , 10.1111/J.1600-079X.1987.TB00835.X