Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies.
Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies.
复制标题
DOI：
10.1007/978-3-642-13443-2_10
复制
发表时间：
2011-01-01
影响因子：
--
通讯作者：
Chern, Yijuang
中科院分区：
文献类型：
--
作者：
Chen, Jiang-Fan;Chern, Yijuang
神经退行性疾病是现代社会中最可怕的疾病之一，没有有效的治疗方法来减缓或阻止这种神经退行性疾病。在最早尝试使用咖啡因治疗帕金森病几十年后，关于咖啡因和腺苷药物对主要神经退行性疾病的潜在益处的大量信息已经积累起来。在这篇综述的第一部分，我们提供了腺苷受体信号系统的一般背景，咖啡因和甲基黄嘌呤通过这些信号系统调节大脑活动，以及它们在神经退行性疾病的发展和治疗中的作用。腺苷受体与其他G蛋白偶联受体和辅助蛋白之间的密切相互作用可能提供有别于腺苷受体单体的药理特性。随后概述了咖啡因和腺苷受体药提供的神经保护防止神经退行性变的主要机制。在第二部分中，我们讨论了咖啡因/甲基黄嘌呤及其主要靶标腺苷受体在包括中风、创伤性脑损伤、阿尔茨海默病、帕金森病、亨廷顿病和多发性硬化症在内的个体神经退行性疾病发展中的研究现状。到目前为止，令人兴奋的发现包括：遗传小鼠模型揭示的腺苷受体在体内的特定功能；在神经退行性疾病的动物模型中长期治疗咖啡因和腺苷受体配体展示了广泛的神经保护作用；几种A(2A)受体选择性拮抗剂的令人鼓舞的发展，这些药物目前正处于帕金森氏病的第三阶段临床试验。重要的是，越来越多的人体和实验研究揭示了令人鼓舞的证据，表明经常摄入咖啡因实际上可能对神经退行性疾病有几个有益的影响，从运动刺激到认知增强到潜在的神经保护。因此，关于神经退行性疾病，甲基黄嘌呤的这些潜在好处，特别是咖啡因，强烈反对临床医生在老龄化人口中阻止人们定期摄入咖啡因的常见做法。
Neurodegenerative disorders are some of the most feared illnesses in modern society, with no effective treatments to slow or halt this neurodegeneration. Several decades after the earliest attempt to treat Parkinson's disease using caffeine, tremendous amounts of information regarding the potential beneficial effect of caffeine as well as adenosine drugs on major neurodegenerative disorders have accumulated. In the first part of this review, we provide general background on the adenosine receptor signaling systems by which caffeine and methylxanthine modulate brain activity and their role in relationship to the development and treatment of neurodegenerative disorders. The demonstration of close interaction between adenosine receptor and other G protein coupled receptors and accessory proteins might offer distinct pharmacological properties from adenosine receptor monomers. This is followed by an outline of the major mechanism underlying neuroprotection against neurodegeneration offered by caffeine and adenosine receptor agents. In the second part, we discuss the current understanding of caffeine/methylxantheine and its major target adenosine receptors in development of individual neurodegenerative disorders, including stroke, traumatic brain injury Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis. The exciting findings to date include the specific in vivo functions of adenosine receptors revealed by genetic mouse models, the demonstration of a broad spectrum of neuroprotection by chronic treatment of caffeine and adenosine receptor ligands in animal models of neurodegenerative disorders, the encouraging development of several A(2A) receptor selective antagonists which are now in advanced clinical phase III trials for Parkinson's disease. Importantly, increasing body of the human and experimental studies reveals encouraging evidence that regular human consumption of caffeine in fact may have several beneficial effects on neurodegenerative disorders, from motor stimulation to cognitive enhancement to potential neuroprotection. Thus, with regard to neurodegenerative disorders, these potential benefits of methylxanthines, caffeine in particular, strongly argue against the common practice by clinicians to discourage regular human consumption of caffeine in aging populations.