摘要
背景:阿尔茨海默病(AD)是全球最常见的痴呆症,2020年美国报告的病例约为600万例。AD的临床表现包括认知功能障碍、冷漠、焦虑和神经精神症状,发病机制涉及淀粉样肽-β细胞外积累和tau蛋白过度磷酸化。不幸的是,目前治疗AD的药物只能缓解症状,而不能逆转AD进展的疾病修饰分子。内源性调节性腺苷通过激活A2A受体,在突触丢失和神经炎症中发挥作用,这对认知障碍和记忆损伤至关重要。 目的:本文将对A2A腺苷受体拮抗剂的最新研究进展进行综述,为未来A2A抑制剂的合理设计提供依据。 方法:本文综述了A2A腺苷受体在AD动物模型和人类模型中的作用及其在突触可塑性和神经炎症中的作用,以及A2A受体在AD动物模型和人类模型中的拮抗作用。此外,还介绍了目前的化学和结构基础策略。 结果:咖啡因,最广泛消费的天然产品兴奋剂和A2A拮抗剂,改善人类的记忆。同样,合成的A2A受体拮抗剂,如本文所述,可能提供一种对抗AD的手段。 结论:这篇综述强调了A2A腺苷受体拮抗剂作为一种治疗AD的新方法的临床潜力。
关键词: 阿尔茨海默病,A2A受体,A2A拮抗剂,认知障碍,药物设计,神经炎症。
Current Medicinal Chemistry
Title:A2A Adenosine Receptor Antagonists in Neurodegenerative Diseases
Volume: 29 Issue: 24
关键词: 阿尔茨海默病,A2A受体,A2A拮抗剂,认知障碍,药物设计,神经炎症。
摘要:
Background: Alzheimer’s disease (AD) is the most common form of dementia worldwide, with approximately 6 million cases reported in America in 2020. The clinical signs of AD include cognitive dysfunction, apathy, anxiety and neuropsychiatric signs, and pathogenetic mechanisms that involve amyloid peptide-β extracellular accumulation and tau hyperphosphorylation. Unfortunately, current drugs to treat AD can provide only symptomatic relief but are not disease-modifying molecules able to revert AD progression. The endogenous modulator adenosine, through A2A receptor activation, plays a role in synaptic loss and neuroinflammation, which are crucial for cognitive impairment and memory damage.
Objective: In this review, recent advances covering A2A adenosine receptor antagonists will be extensively reviewed, providing a basis for the rational design of future A2A inhibitors.
Methods: Herein, the literature on A2A adenosine receptors and their role in synaptic plasticity and neuroinflammation, as well as the effects of A2A antagonism in animal models of AD and in humans, are reviewed. Furthermore, current chemical and structure-based strategies are presented.
Results: Caffeine, the most widely consumed natural product stimulant and an A2A antagonist, improves human memory. Similarly, synthetic A2A receptor antagonists, as described in this review, may provide a means to fight AD.
Conclusion: This review highlights the clinical potential of A2A adenosine receptor antagonists as a novel approach to treat patients with AD.
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Cite this article as:
A2A Adenosine Receptor Antagonists in Neurodegenerative Diseases, Current Medicinal Chemistry 2022; 29 (24) . https://dx.doi.org/10.2174/0929867328666211129122550
DOI https://dx.doi.org/10.2174/0929867328666211129122550 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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