Neurodegenerative disease encompasses a wide range of disorders afflicting the central and peripheral nervous systems and is a major unmet biomedical need of our time. There are very limited treatments, and no cures, for most of these diseases, including Alzheimer's Disease, Parkinson's Disease, Huntington Disease, and Motor Neuron Diseases. Mouse and other animal models provide hope by analysing them to understand pathogenic mechanisms, to identify drug targets, and to develop gene therapies and stem cell therapies. However, despite many decades of research, virtually no new treatments have reached the clinic. Increasingly, it is apparent that human heterogeneity within clinically defined neurodegenerative disorders, and between patients with the same genetic mutations, significantly impacts disease presentation and, potentially, therapeutic efficacy. Therefore, stratifying patients according to genetics, lifestyle, disease presentation, ethnicity, and other parameters may hold the key to bringing effective therapies from the bench to the clinic. Here, we discuss genetic and cellular humanised mouse models, and how they help in defining the genetic and environmental parameters associated with neurodegenerative disease, and so help in developing effective precision medicine strategies for future healthcare.

中文翻译：

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人源化小鼠模型在神经退行性疾病精准医学中的应用。

神经退行性疾病涵盖了影响中枢和周围神经系统的多种疾病，是我们这个时代未满足的主要生物医学需求。大多数这些疾病的治疗方法非常有限，并且无法治愈，包括阿尔茨海默病、帕金森病、亨廷顿病和运动神经元病。小鼠和其他动物模型通过分析它们来了解致病机制、识别药物靶点以及开发基因疗法和干细胞疗法，从而提供了希望。然而，尽管进行了数十年的研究，实际上还没有新的治疗方法进入临床。越来越明显的是，临床定义的神经退行性疾病中的人类异质性以及具有相同基因突变的患者之间的异质性显着影响疾病表现并可能影响治疗效果。因此，根据遗传学、生活方式、疾病表现、种族和其他参数对患者进行分层可能是将有效疗法从实验室带到临床的关键。在这里，我们讨论遗传和细胞人源化小鼠模型，以及它们如何帮助定义与神经退行性疾病相关的遗传和环境参数，从而帮助为未来的医疗保健制定有效的精准医疗策略。