Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer＇s disease  

作　　者：Zhi-zhong GUAN 

机构地区：[1]Department of Molecular Biology and Pathology, G.iyang Medical University, Guiyang 550004, China

出　　处：《Acta Pharmacologica Sinica》2008年第7期773-780,共8页中国药理学报（英文版）

基　　金：This work was supported financially by grants from the Foundation of Ministry of Science and Technology of China （No 2004DFB02800 and 2006DFA33530）, the Chinese National Natural Science Foundation （No 30460045）. and the Foundation of Guizhou Province of China （No [2006] 400107, [2006] 52, and [2006] 6015）.

摘　　要：Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play important roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors （nAChRs）, muscarinic receptors （mAChRs）, and N-methyl-D-aspartate （NMDA） receptors, exhibiting disturbances of cellular membrane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physiological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information for understanding the correlation between oxidative stress and changed cholinergic and glutaminergic receptors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play important roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors （nAChRs）, muscarinic receptors （mAChRs）, and N-methyl-D-aspartate （NMDA） receptors, exhibiting disturbances of cellular membrane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physiological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information for understanding the correlation between oxidative stress and changed cholinergic and glutaminergic receptors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.

关 键 词：Alzheimer＇s disease oxidative stress nicotinicreceptor muscarinic receptor N-methyl-D-aspartate receptor 

分 类 号：R749.16[医药卫生—神经病学与精神病学]