Alzheimer's disease (AD) is a neurodegenerative disorder which accounts for 60-70% of the 50 million worldwide cases of dementia and is characterised by cognitive impairments, many of which have long been associated with dysfunction of the cholinergic system. Although the M1 muscarinic acetylcholine receptor (mAChR) is considered a promising drug target for AD, ligands targeting this receptor have so far been unsuccessful in clinical trials. As modulatory receptors to cholinergic transmission, the endocannabinoid system may be a promising drug target to allow fine tuning of the cholinergic system. Furthermore, disease-related changes have been found in the endocannabinoid system during AD progression and indeed targeting the endocannabinoid system at specific disease stages alleviates cognitive symptoms in numerous mouse models of AD. Here we review the role of the endocannabinoid system in AD, and its crosstalk with mAChRs as a potential drug target for cholinergic dysfunction.

中文翻译：

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M1 毒蕈碱乙酰胆碱受体和内源性大麻素系统之间的串扰：与阿尔茨海默氏病的相关性？


阿尔茨海默病 (AD) 是一种神经退行性疾病，占全球 5000 万痴呆病例的 60-70%，其特点是认知障碍，其中许多障碍长期以来与胆碱能系统功能障碍有关。尽管 M1 毒蕈碱乙酰胆碱受体 (mAChR) 被认为是治疗 AD 的有希望的药物靶点，但针对该受体的配体迄今为止在临床试验中尚未成功。作为胆碱能传递的调节受体，内源性大麻素系统可能是一个有前途的药物靶点，可以对胆碱能系统进行微调。此外，在 AD 进展过程中，内源性大麻素系统也发生了与疾病相关的变化，并且在特定疾病阶段针对内源性大麻素系统确实可以缓解许多 AD 小鼠模型的认知症状。在这里，我们回顾了内源性大麻素系统在 AD 中的作用，及其与 mAChR 的串扰作为胆碱能功能障碍的潜在药物靶点。