Nicotinic receptor-mediated protection against β-amyloid neurotoxicity

被引:95
作者
Shimohama, S [1 ]
Kihara, T [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 606, Japan
关键词
Alzheimer's disease; nicotine; nicotinic receptor; beta-amyloid; glutamate; protection;
D O I
10.1016/S0006-3223(00)01100-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Multiple lines of evidence, from molecular and cellular to epidemiologic, have implicated nicotinic transmission in the pathology of Alzheimer's disease. In this review we present evidence for nicotinic receptor-mediated protection against beta -amyloid and glutamate neurotoxicity, and the signal transduction involved in this mechanism. The data are based mainly on our studies using rat-cultured primary neurons. Nicotine-induced protection was blocked by an alpha7 nicotinic receptor antagonist, a phosphatidylinositol 3-kinase inhibitor, and an Src inhibitor. Levels of phosphorylated Akt, an effector of phosphatidylinositol 3-kinase; Bcl-2; and Bcl-x were increased by nicotine administration. From these experimental data, our hypothesis for the mechanism of nicotinic receptor-mediated survival signal transduction is that the alpha7 nicotinic receptor stimulates the Src family, which activates phosphatidylinositol 3-kinase to phosphorylate Akt, which subsequently transmits the signal to upregulate Bcl-2 and Bcl-x. Upregulation of Bcl-2 and Bcl-x could prevent cells from neuronal death induced by beta -amyloid and glutamate. These findings suggest that an early diagnosis of Alzheimer's disease and protective therapy with nicotinic receptor stimulation could delay the progress of Alzheimer's disease. (C) 2001 Society of Biological Psychiatry.
引用
收藏
页码:233 / 239
页数:7
相关论文
共 50 条
[31]   Inhibition of nicotinic receptor-mediated catecholamine secretion by Dryobalanops aromatica in bovine adrenal chromaffin cells [J].
Oh, KS ;
Park, TJ ;
Choi, BH ;
Lee, DK ;
Lee, TK ;
Kim, KT .
PHARMACOLOGICAL RESEARCH, 2000, 42 (06) :559-564
[32]   DIRECT MUSCARINIC AND NICOTINIC RECEPTOR-MEDIATED EXCITATION OF RAT MEDIAL VESTIBULAR NUCLEUS NEURONS INVITRO [J].
PHELAN, KD ;
GALLAGHER, JP .
SYNAPSE, 1992, 10 (04) :349-358
[33]   BLOCKADE OF NICOTINIC RECEPTOR-MEDIATED RELEASE OF DOPAMINE FROM STRIATAL SYNAPTOSOMES BY CHLORISONDAMINE AND OTHER NICOTINIC ANTAGONISTS ADMINISTERED IN-VITRO [J].
ELBIZRI, H ;
CLARKE, PBS .
BRITISH JOURNAL OF PHARMACOLOGY, 1994, 111 (02) :406-413
[34]   NONCOMPETITIVE ANTAGONISM BY HIRSUTEINE OF NICOTINIC RECEPTOR-MEDIATED DOPAMINE RELEASE FROM RAT PHEOCHROMOCYTOMA CELLS [J].
WATANO, T ;
NAKAZAWA, K ;
OBAMA, T ;
MORI, M ;
INOUE, K ;
FUJIMORI, K ;
TAKANAKA, A .
JAPANESE JOURNAL OF PHARMACOLOGY, 1993, 61 (04) :351-356
[35]   Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons [J].
Kanki, R ;
Nakamizo, T ;
Yamashita, H ;
Kihara, T ;
Sawada, H ;
Uemura, K ;
Kawamata, J ;
Shibasaki, H ;
Akaike, A ;
Shimohama, S .
BRAIN RESEARCH, 2004, 1015 (1-2) :73-81
[36]   Receptor-Mediated Abeta Amyloid Antibody Targeting to Alzheimer's Disease Mouse Brain [J].
Zhou, Qing-Hui ;
Fu, Ailing ;
Boado, Ruben J. ;
Hui, Eric Ka-Wai ;
Lu, Jeff Zhiqiang ;
Pardridge, William M. .
MOLECULAR PHARMACEUTICS, 2011, 8 (01) :280-285
[37]   BETA-AMYLOID NEUROTOXICITY IN HUMAN CORTICAL CULTURE IS NOT MEDIATED BY EXCITOTOXINS [J].
BUSCIGLIO, J ;
YEH, J ;
YANKNER, BA .
JOURNAL OF NEUROCHEMISTRY, 1993, 61 (04) :1565-1568
[38]   Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism [J].
Miller, DK ;
Wilkins, LH ;
Bardo, MT ;
Crooks, PA ;
Dwoskin, LP .
PSYCHOPHARMACOLOGY, 2001, 156 (04) :469-476
[39]   Neuroprotective effect of genistein against beta amyloid-induced neurotoxicity [J].
Bang, OY ;
Hong, HS ;
Kim, DH ;
Kim, H ;
Boo, JH ;
Huh, K ;
Mook-Jung, I .
NEUROBIOLOGY OF DISEASE, 2004, 16 (01) :21-28
[40]   Protective effects of wogonoside against β-amyloid-induced neurotoxicity and neuroinflammation [J].
Jin, Meifang ;
Zhang, Min ;
Zhao, He ;
Xu, Lixiao ;
Su, Guanghao ;
Li, Gang .
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2017, 10 (10) :14350-14358