The molecular processes underlying neurodegenerative diseases (such as Alzheimer's Disease - AD) remain poorly understood. There is also an imperative need for disease-modifying therapies in AD since the present treatments, acetylcholinesterase inhibitors and NMDA antagonists, do not halt its progression. AD and other dementias present unique pathological features such as that of microtubule associated protein tau metabolic regulation. Tau has numerous binding partners, including signaling molecules, cytoskeletal elements and lipids, which suggests that it is a multifunctional protein. AD has also been associated with severe loss of cholinergic markers in the brain and such loss may be due to the toxic interaction of tau with cholinergic muscarinic receptors. By using specific antagonists of muscarinic receptors it was found in vitro that extracellular tau binds to M1 and M3 receptors and which the increase of intracellular calcium found in neuronal cells upon tau-binding. However, so far, the significance of tau signaling through muscarinic receptor in vivo in tauopathic models remains uncertain. The data reviewed in the present paper highlight the significant effect of M1 receptor/tau interaction in exacerbating tauopathy related pathological features and suggest that selective M1 agonists may serve as a prototype for future therapeutic development toward modification of currently intractable neurodegenerative diseases, such as tauopathies.

神经退行性疾病（例如阿尔茨海默氏病-AD）的分子过程仍然知之甚少。还迫切需要AD中的疾病改善疗法，因为本发明的治疗方法，乙酰胆碱酯酶抑制剂和NMDA拮抗剂，不会阻止其发展。AD和其他痴呆症表现出独特的病理学特征，例如微管相关蛋白tau代谢调节。Tau具有许多结合伴侣，包括信号分子，细胞骨架成分和脂质，这表明它是一种多功能蛋白质。AD还与脑中胆碱能标志物的严重丧失有关，这种丧失可能是由于tau与胆碱能毒蕈碱受体的毒性相互作用。通过使用毒蕈碱受体的特异性拮抗剂，在体外发现胞外tau与M1和M3受体结合，并且在tau结合后神经元细胞中发现胞内钙的增加。然而，到目前为止，在tauopathic模型中通过毒蕈碱受体体内tau信号传导的重要性仍不确定。本文审查的数据突出了M1受体/ tau相互作用在加重tauopathy相关病理特征方面的显著作用，并表明选择性M1激动剂可作为未来治疗发展的原型，以朝着目前顽固的神经退行性疾病（如tauopathies）的修饰方向发展。在陶氏病模型中体内通过毒蕈碱受体传递tau信号的重要性尚不确定。本文审查的数据突出了M1受体/ tau相互作用在加重tauopathy相关病理特征方面的显著作用，并表明选择性M1激动剂可作为未来治疗发展的原型，以朝着目前顽固的神经退行性疾病（如tauopathies）的修饰方向发展。在陶氏病模型中通过毒蕈碱受体体内tau信号传导的重要性尚不确定。本文审查的数据突出了M1受体/ tau相互作用在加重tauopathy相关病理特征方面的显著作用，并表明选择性M1激动剂可作为未来治疗发展的原型，以朝着目前顽固的神经退行性疾病（如tauopathies）的修饰方向发展。