Is there nicotinic modulation of nerve growth factor? Implications for cholinergic therapies in Alzheimer's disease
Is there nicotinic modulation of nerve growth factor? Implications for cholinergic therapies in Alzheimer's disease
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DOI：
10.1016/s0006-3223(00)01047-7
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发表时间：
2001-02-01
影响因子：
10.6
通讯作者：
Rattray, M
中科院分区：
文献类型：
--
作者：
Rattray, M
神经生长因子（NGF）的神经生物学研究揭示了其多种作用。通过基因表达的改变，NGF在维持和调节表达高亲和力受体trkA的神经元表型中起重要作用。神经生长因子在膀胱和皮肤疼痛信号传导中也具有快速作用。在中枢神经系统（CNS）中，NGF与胆碱能系统有着密切的关系。它促进实验损伤后胆碱能神经元的存活，并维持和调节未损伤的胆碱能神经元的表型。除了这些由基因表达介导的作用外，NGF还具有快速的神经递质样作用，可调节胆碱能神经传递和神经元兴奋性。与其对胆碱能系统的作用一致，NGF可以增强胆碱能病变动物的功能，并被认为对阿尔茨海默病（AD）患者有用；然而，中枢神经系统传递的问题和副作用（特别是疼痛）限制了NGF的临床疗效。增强中枢神经系统中NGF产生的药物治疗策略可能有助于治疗AD。尼古丁就是这样一种物质，当它直接作用于大鼠的海马体时，会产生长期的神经生长因子的增加。(C) 2001年生物精神病学学会。
Studies on the neurobiology of nerve growth factor (NGF) reveal a diverse range of actions. Through alterations in gene expression, NGF is important in maintaining and regulating the phenotype of neurons that express the high-affinity receptor, trkA. Nerve growth factor also has a rapid action, revealed by its role in pain signaling in bladder and in skin. In the central nervous system (CNS), NGF has an intimate relationship with the cholinergic system. It promotes cholinergic neuron survival after experimental injury but also maintains and regulates the phenotype of uninjured cholinergic neurons. In addition to these effects mediated by gene expression, NGF has a rapid neurotransmitter-like action to regulate cholinergic neurotransmission and neuronal excitability. Consistent with its actions on the cholinergic system, NGF can enhance function in animals with cholinergic lesions and has been proposed to be useful in humans with Alzheimer's disease (AD); however, the problems of CNS delivery and side effects (particularly pain) limit the clinical efficacy of NGF. Drug treatment strategies to enhance production of NGF in the CNS may be useful in the treatment of AD. Nicotine is one such agent, which, when administered directly to the hippocampus in rats, produces long-lasting elevation of NGF production. (C) 2001 Society of Biological Psychiatry.