内源性大麻素系统与老年性痴呆

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (8): 943-947.

内源性大麻素系统与老年性痴呆

董满满, 杨红卫

三峡大学医学院生理学教研室,宜昌 443002,湖北

收稿日期:2013-10-07 修回日期:2014-06-25 出版日期:2014-08-26 发布日期:2014-08-26
通讯作者: 杨红卫,男,博士,教授。研究方向:神经药理学。 Tel: 0717-6397620 E-mail: yhwctgu@sina.com
作者简介:董满满,女,硕士研究生。研究方向:内源性大麻素对神经元损害的保护作用及其机制的研究。 Tel: 15071798501 E-mail: ctguviolet@163.com

Endogenous cannabinoid system and Alzheimer Disease

DONG Man-man, YANG Hong-wei

Department of Physiology, College of Medical Sciences of China Three Gorges University, Yichang 443002,Hubei,China

Received:2013-10-07 Revised:2014-06-25 Online:2014-08-26 Published:2014-08-26

摘要/Abstract

摘要： 老年性痴呆即阿尔茨海默病(Alzheimer's disease, AD)是一种慢性进行性的神经退行性病变,其特征性病理改变为β-淀粉样蛋白(β-amyloid peptide, Aβ)沉积形成的细胞外老年斑和tau蛋白过度磷酸化形成的神经细胞内神经原纤维缠结,以及神经元丢失伴随胶质细胞增生等。最近的研究发现内源性大麻素系统对AD的病程有预防治疗作用,主要基于其对神经的保护作用和抗炎功效。本文综述了内源性大麻素对AD的保护作用的几个方面,旨在为AD的治疗开辟新的策略和思路。

关键词: 内源性大麻素系统, 2-花生四烯酸甘油, 大麻素受体, 老年性痴呆

Abstract: Alzheimer's disease (AD) is a chronic progressing neurodegenerative disorder, and the principal neuropathological hallmark of the disease, is the extracellular β-amyloid peptide(Aβ) accumu- lation formed senile plaques, intracellular hyperphosphorylated tau formed neurofibrillary tangles, and loss of neuron with gliocyte proliferation. Recent evidence shows that endogenous cannabinoid system serve as preventive treatment for AD, based on their neuroprotective and anti-inflammatory effects. Here we summarizes several aspects of the endogenous cannabinoid protective effect of the AD, aiming at providing a new method for the treatment of AD.

Key words: endogenous cannabinoid system, 2-Arachidonoylglycerol, cannabinoid receptor, Alzheimer's disease

中图分类号:

R338
R322

董满满, 杨红卫. 内源性大麻素系统与老年性痴呆[J]. 中国临床药理学与治疗学, 2014, 19(8): 943-947.

DONG Man-man, YANG Hong-wei. Endogenous cannabinoid system and Alzheimer Disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(8): 943-947.

参考文献 31

[1]	张玉琦,徐文炜,程灶火,等. 多奈哌齐合并奥氮平治疗老年痴呆精神行为症状的疗效和安全性对照研究[J] . 中国临床药理学与治疗学, 2012 , 17(9): 1038-1041.
[2]	Lee JH, Agacinski G, Williams JH, et al.Intact cannabinoid CB1 receptors in the Alzheimer's disease cortex[J]. Neurochem Int,2010, 57(8): 985-989.
[3]	Van der Stelt M, Mazzola C, Esposito G,et al. Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels[J]. Cell Mol Life Sci, 2006, 63(12): 1410-1424.
[4]	Tanveer R, Gowran A, Noonan J, et al.The Endocannabinoid, Anandamide, Augments Notch-1 Signaling in Cultured Cortical Neurons Exposed to Amyloid-β and in the Cortex of Aged Rats[J]. J Biol Chem, 2012, 287(41): 34709-34721.
[5]	Bachmeier C, Beaulieu-Abdelahad D, Mullan M, et al.Role of the cannabinoid system in the transit of beta-amyloid across the blood-brain barrier[J]. Mol Cell Neurosci, 2013, 56: 255-262.
[6]	Chen R, Zhang J, Wu Y, et al.Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease[J]. Cell Rep, 2012, 2(5): 1329-1339.
[7]	Wu J, Bie B, Yang H, et al.Activation of the CB2 receptor system reverses amyloid-induced memory deficiency[J]. Neurobiol Aging, 2013, 34(9): 791-804.
[8]	Mulder J, Zilberter M, Pasquaré SJ, et al.Molecular reorganization of endocannabinoid signalling in Alzheimer's disease[J]. Brain, 2011, 134(4): 1041-1060.
[9]	Ozaita A, Puighermanal E, Maldonado R.Regulation of PI3K/Akt/GSK‐3 pathway by cannabinoids in the brain[J]. J Neurochem, 2007, 102(4): 1105-1114.
[10]	Scotter EL, Abood ME, Glass M.The endocannabinoid system as a target for the treatment of neurodegenerative disease[J]. Br J Pharmacol, 2010, 160(3): 480-498.
[11]	Zhang L, Wang M, Bisogno T, et al.Endocannabinoids Generated by Ca2+ or by Metabotropic Glutamate Receptors Appear to Arise from Different Pools of Diacylglycerol Lipase[J]. PLoS One, 2011, 6(1): e16305.
[12]	Ohno-Shosaku T, Tanimura A, Hashimotodani Y, et al.Endocannabinoids and retrograde modulation of synaptic transmission[J]. Neuroscientist, 2012, 18(2): 119-132.
[13]	Van Sickle MD, Duncan M, Kingsley PJ, et al.Identification and functional characterization of brainstem cannabinoid CB2 receptors[J]. Science, 2005, 310(5746): 329-332.
[14]	马晓飞. β-淀粉样蛋白与老年痴呆症[J]. 中国医药导报, 2011, 8(15): 13-15.
[15]	Gauthier A, Vassiliou G, Benoist F, et al.Adipocyte low density lipoprotein receptor-related protein gene expression and function is regulated by peroxisome proliferator-activated receptor γ[J]. J Biol Chem, 2003, 278(14): 11945-11953.
[16]	Martin-Moreno AM, Brera B, Spuch C, et al.Prolonged oral cannabinoid administration prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in Tg APP 2576 mice[J]. J Neuroinflammation, 2012, 9: 8.
[17]	Tolón RM, Núñez E, Pazos MR, et al.The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages[J]. Brain Res, 2009, 1283: 148-154.
[18]	Blanco A, Alvarez S, Fresno M, et al.Amyloid-β induces cyclooxygenase-2 and PGE2 release in human astrocytes in NF-kB dependent manner[J]. J Alzheimers Dis,2010, 22(2): 493-505.
[19]	Chen X, Zhang J, Chen C.Endocannabinoid 2-arachidonoylglycerol protects neurons against β-amyloid insults[J]. Neuroscience, 2011, 178: 159-168.
[20]	Jung KM, Astarita G, Yasar S, et al.An amyloid β42-dependent deficit in anandamide mobilization is associated with cognitive dysfunction in Alzheimer's disease[J]. Neurobiol Aging, 2012, 33(8): 1522-1532.
[21]	Piro JR, Benjamin DI, Duerr JM, et al.A dysregulated endocannabinoid-eicosanoid network supports pathogenesis in a mouse model of Alzheimer's disease[J]. Cell reports, 2012, 1(6): 617-623.
[22]	Harvey BS, Ohlsson KS, Mååg JL, et al.Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro[J]. Neurotoxicology, 2012, 33(1): 138-146.
[23]	Haghani M, Shabani M, Javan M, et al.CB1 cannabinoid receptor activation rescues amyloid β-induced alterations in behaviour and intrinsic electrophysiological properties of rat hippocampal CA1 pyramidal neurons[J]. Cell Physiol Biochem, 2012, 29(3/4): 391-406.
[24]	Mazzola C, Micale V, Drago F.Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade[J]. Eur J Pharmacol, 2003, 477(3): 219-225.
[25]	Micale V, Cristino L, Tamburella A, et al.Enhanced cognitive performance of dopamine D3 receptor "knock-out" mice in the step-through passive-avoidance test: assessing the role of the endocannabinoid/endovanilloid systems[J]. Pharmacol Res, 2010, 61(6): 531-536.
[26]	Aso E, Juvés S, Maldonado R, et al.CB2 Cannabinoid Receptor Agonist Ameliorates Alzheimer-Like Phenotype in AβPP/PS1 Mice[J]. J Alzheimers Dis, 2013, 35(4): 847-858.
[27]	Wolff MC, Leander JD.SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task[J]. Eur Pharmacol, 2003, 477(3): 213-217.
[28]	Shemer I, Holmgren C, Min R, et al.Non‐fibrillar β‐amyloid abates spike‐timing‐dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors[J]. Eur Journal Neurosci, 2006, 23(8): 2035-2047.
[29]	Tanimura A, Yamazaki M, Hashimotodani Y, et al.The endocannabinoid 2-arachidono- ylglycerol produced by diacylglycerol lipase α mediates retrograde suppression of synaptic transmission[J]. Neuron, 2010, 65(3): 320-327.
[30]	Blalock EM, Geddes JW, Chen KC, et al.Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses[J]. Proc Natl Acad Sci USA, 2004, 101(7): 2173-2178.
[31]	Mateo I, Infante J, Llorca J, et al.Association between glycogen synthase kinase-3beta genetic polymorphism and late-onset Alzheimer 's disease[J]. Dement Geriatr Cogn Disord, 2006, 21(4): 228-232.