Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave, North, Worcester, MA, 01655, USA.
Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Ave, North, Worcester, MA, 01655, USA.
Neurotherapeutics. 2019 Apr;16(2):299-313. doi: 10.1007/s13311-019-00710-x.
Stroke remains a leading cause of disability and death worldwide despite significant scientific and therapeutic advances. Therefore, there is a critical need to improve stroke prevention and treatment. In this review, we describe several examples that leverage nucleic acid therapeutics to improve stroke care through prevention, acute treatment, and recovery. Aptamer systems are under development to increase the safety and efficacy of antithrombotic and thrombolytic treatment, which represent the mainstay of medical stroke therapy. Antisense oligonucleotide therapy has shown some promise in treating stroke causes that are genetically determined and resistant to classic prevention approaches such as elevated lipoprotein (a) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Targeting microRNAs may be attractive because they regulate factors involved in neuronal cell death and reperfusion-associated injury, as well as neurorestorative pathways. Lastly, microRNAs may aid reliable etiologic classification of stroke subtypes, which is important for effective secondary stroke prevention.
尽管在科学和治疗方面取得了重大进展,但中风仍然是全球范围内导致残疾和死亡的主要原因。因此,迫切需要改善中风的预防和治疗。在这篇综述中,我们描述了一些利用核酸疗法通过预防、急性治疗和恢复来改善中风治疗的例子。适体系统正在开发中,以提高抗血栓和溶栓治疗的安全性和有效性,这是医学中风治疗的主要方法。反义寡核苷酸疗法在治疗由遗传决定且对经典预防方法(如升高的脂蛋白(a)和伴有皮质下梗死和白质脑病的脑常染色体显性动脉病(CADASIL))有抗性的中风病因方面显示出一定的前景。靶向 microRNAs 可能很有吸引力,因为它们调节涉及神经元细胞死亡和再灌注相关损伤以及神经修复途径的因素。最后,microRNAs 可能有助于中风亚型的可靠病因分类,这对于有效的二级中风预防很重要。