Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review.
Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review.
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DOI：
10.1016/j.lfs.2014.01.083
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发表时间：
2014-04-17
期刊：
影响因子：
6.1
通讯作者：
Diaz-Rios, Manuel
中科院分区：
文献类型：
--
作者：
Rivera-Oliver, Marla;Diaz-Rios, Manuel
咖啡因是世界上消耗最多的精神兴奋剂，它被认为会影响基本和基本的人类过程，如睡眠，觉醒，认知，学习和记忆。作为腺苷受体（A1、A2 a、A2 b和A3）的非选择性阻断剂，与心率调节、心脏和平滑肌收缩/舒张以及中枢神经系统（CNS）中的神经信号传导有关。自20世纪90年代后期以来，使用腺苷受体拮抗剂（如咖啡因）阻断A1和A2 a腺苷受体亚型的研究已显示出减少由脊髓损伤（SCI）或中风（脑梗塞）以及由其他神经退行性疾病（如帕金森病和阿尔茨海默病）引起的物理、细胞和分子损伤。有趣的是，使用腺苷受体激动剂的其他研究也显示通过减少兴奋性神经递质释放、细胞凋亡和炎症反应等，对神经退行性疾病的各种模型提供神经保护作用。腺苷受体激动剂和拮抗剂作为神经保护剂的看似矛盾的用途已归因于剂量水平、药物递送方法、兴奋性神经递质的细胞外浓度和疾病进展阶段的差异。我们讨论和比较最近的研究结果，使用腺苷受体拮抗剂和激动剂的动物模型和患者遭受脊髓损伤，脑中风，帕金森氏症和阿尔茨海默氏症。此外，我们提出了替代解释这些药物作为潜在的药理学工具来治疗这些不同类型的神经退行性疾病的看似矛盾的使用。
Caffeine is the most consumed pychostimulant in the world, and it is known to affect basic and fundamental human processes such as sleep, arousal, cognition and learning and memory. It works as a nonselective blocker of adenosine receptors (A1, A2a, A2b and A3) and has been related to the regulation of heart rate, the contraction/relaxation of cardiac and smooth muscles, and the neural signaling in the central nervous system (CNS). Since the late 1990s, studies using adenosine receptor antagonists, such as Caffeine, to block the A1 and A2a adenosine receptor subtypes have shown to reduce the physical, cellular and molecular damages caused by a spinal cord injury (SCI) or a stroke (cerebral infarction) and by other neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Interestingly, other studies using adenosine receptor agonists have also shown to provide a neuroprotective effect on various models of neurodegenerative diseases through the reduction of excitatory neurotransmitter release, apoptosis and inflammatory responses, among others. The seemingly paradoxical use of both adenosine receptor agonists and antagonists as neuroprotective agents has been attributed to differences in dosage levels, drug delivery method, extracellular concentration of excitatory neurotransmitters and stage of disease progression. We discuss and compare recent findings using both antagonists and agonists of adenosine receptors in animal models and patients that have suffered spinal cord injuries, brain strokes, and Parkinson's and Alzheimer's diseases. Additionally, we propose alternative interpretations on the seemingly paradoxical use of these drugs as potential pharmacological tools to treat these various types of neurodegenerative diseases.
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DOI：
10.3233/jad-2009-1071
发表时间：
2009
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cao C;Cirrito JR;Lin X;Wang L;Verges DK;Dickson A;Mamcarz M;Zhang C;Mori T;Arendash GW;Holtzman DM;Potter H
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Potter H
影响因子：
4
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通讯作者：
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影响因子：
2.9
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1111/j.1530-0277.2011.01586.x
发表时间：
2012-01
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Butler TR;Prendergast MA
通讯作者：
Prendergast MA