In recent years there has been a renewed interest in the basal forebrain (BF) cholinergic system as a target for the treatment of cognitive impairments in patients with Parkinson´s disease (PD), due in part to the need to explore novel approaches to treat the cognitive symptoms of the disease, and in part to the development of more refined imaging tools that have made it possible to monitor the progressive changes in the structure and function of the BF system as they evolve over time. In parallel, emerging technologies allowing the derivation of authentic BF cholinergic neurons from human pluripotent stem cells are providing new powerful tools for the exploration of cholinergic neuron replacement in animal models of PD-like cognitive decline. In this review, we discuss the rationale for cholinergic cell replacement as a potential therapeutic strategy in PD and how this approach can be explored in rodent models of PD-like cognitive decline, building on insights gained from the extensive animal experimental work that was performed in rodent and primate models in the 1980s and 90 s. Although therapies targeting the cholinergic system has so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the BF system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost BF cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

中文翻译：

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基底前脑胆碱能系统作为帕金森病细胞替代疗法的靶点

近年来，人们对将基底前脑 (BF) 胆碱能系统作为治疗帕金森病 (PD) 患者认知障碍的目标重新产生了兴趣，部分原因是需要探索新的治疗方法疾病的认知症状，部分归功于更精细的成像工具的开发，这些工具使得监测 BF 系统的结构和功能随着时间的推移而发生的逐渐变化成为可能。与此同时，新兴技术允许从人类多能干细胞中衍生出真正的 BF 胆碱能神经元，为探索 PD 样认知衰退动物模型中的胆碱能神经元替代提供了新的强大工具。在这篇综述中，我们基于从广泛的动物实验工作中获得的见解，讨论了胆碱能细胞替代作为 PD 潜在治疗策略的基本原理，以及如何在 PD 样认知衰退的啮齿动物模型中探索这种方法。 20世纪80年代和90年代的啮齿动物和灵长类动物模型。尽管迄今为止针对胆碱能系统的治疗主要集中在阿尔茨海默病患者身上，但伴有痴呆的帕金森病可能是一种更相关的疾病。在患有痴呆症的 PD 中，BF 系统会发生进行性退化，并且胆碱能细胞损失的程度已被证明与认知障碍的程度相关。因此，旨在替代丢失的 BF 胆碱能神经元的细胞疗法代表了一种有趣的策略，可以对抗 PD 痴呆患者的一些主要认知障碍。