University of Texas Medical School at Houston, Houston, Texas, 77030, USA.
Curr Pharm Des. 2012;18(8):1148-58. doi: 10.2174/138161212799315768.
Neurodegenerative diseases (NDs) are some of the most debilitating human illnesses. Research over the past 10 years has provided evidence for a common mechanism of neurodegeneration in which the critical event is the brain accumulation of misfolded protein aggregates. Although it is well established that misfolded proteins play an important role in these diseases, the mechanisms by which they cause cellular and tissue dysfunction are still unknown. To understand the molecular basis of NDs and to develop therapeutic strategies against them, numerous transgenic rodent models have been produced, which reproduce some (but not all) of the features of these diseases. Importantly, some NDs are not exclusive to human beings, such as transmissible spongiform encephalopathies. Moreover, other diseases which are associated to aging (e.g. Alzheimer's disease) could be studied in aged mammals, which could reproduce the human disease in a more natural way. Although the usefulness of transgenic mice is unquestionable, the information obtained from natural non-transgenic models could be very valuable to fully understand the pathogenesis of these devastating diseases.
神经退行性疾病（NDs）是一些最使人虚弱的人类疾病。在过去的 10 年中，研究已经提供了神经退行性变的共同机制的证据，其中关键事件是大脑中错误折叠的蛋白质聚集体的积累。尽管已经证实错误折叠的蛋白质在这些疾病中起着重要作用，但它们导致细胞和组织功能障碍的机制尚不清楚。为了了解 NDs 的分子基础并开发针对它们的治疗策略，已经产生了许多转基因啮齿动物模型，这些模型再现了这些疾病的一些（但不是全部）特征。重要的是，一些 NDs 并不仅限于人类，例如传染性海绵状脑病。此外，与衰老相关的其他疾病（例如阿尔茨海默病）可以在老年哺乳动物中进行研究，这可以以更自然的方式再现人类疾病。尽管转基因小鼠的用途是毋庸置疑的，但从天然非转基因模型中获得的信息对于充分了解这些破坏性疾病的发病机制可能非常有价值。
