Cellular and Molecular Neurobiology Area, Viral Vector Core and Gene Therapy, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia, Medellin, Colombia.
Rev Neurosci. 2011;22(2):143-52. doi: 10.1515/RNS.2011.015.
Neurodegeneration is one of the greatest public health challenges for the 21st century. Among neurodegenerative diseases, Alzheimer's disease (AD) is the most prevalent and best characterized. Nevertheless, despite the large investment in AD research, currently there is no effective therapeutic option. In the present review, we highlight a novel alternative, which takes advantage of the biotechnological outbreak deployed by the discovery of the RNA interference-based gene silencing mechanism, and its application as a tool for neurodegeneration treatment. Here, we highlight cyclin-dependent kinase 5 (CDK5) as a key candidate target for therapeutic gene silencing. Unlike other members of the cyclin-dependent kinase family, CDK5 does not seem to play a crucial role in cell cycle regulation. By contrast, CDK5 participates in multiple functions during nervous system development and has been established as a key mediator of Tau hyperphosphorylation and neurofibrillary pathology, thus serving as an optimal candidate for targeted therapy in the adult nervous system. We propose that the use of RNA interference for CDK5 silencing presents an attractive and specific therapeutic alternative for AD and perhaps against other tauopathies.
神经退行性疾病是 21 世纪最大的公共健康挑战之一。在神经退行性疾病中，阿尔茨海默病（AD）是最常见和特征最明确的一种。然而，尽管在 AD 研究方面投入了大量资金，但目前尚无有效的治疗方法。在本综述中，我们强调了一种新的替代方法，该方法利用 RNA 干扰为基础的基因沉默机制的生物技术突破及其在神经退行性疾病治疗中的应用。在这里，我们强调周期蛋白依赖性激酶 5（CDK5）作为治疗性基因沉默的关键候选靶点。与细胞周期蛋白依赖性激酶家族的其他成员不同，CDK5 似乎在细胞周期调控中不起关键作用。相反，CDK5 在神经系统发育过程中参与多种功能，并已被确立为 Tau 过度磷酸化和神经纤维病理的关键介质，因此成为成年神经系统靶向治疗的理想候选药物。我们提出，使用 RNA 干扰进行 CDK5 沉默为 AD 乃至其他 Tau 病提供了一种有吸引力的、特异性的治疗选择。
