Niccolini Benedetta, Palmieri Valentina, De Spirito Marco, Papi Massimiliano
Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Fondazione Policlinico Universitario "A. Gemelli" IRCSS, 00168 Rome, Italy.
Materials (Basel). 2021 Dec 24;15(1):126. doi: 10.3390/ma15010126.
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration and death of motor neurons. This neurodegenerative disease leads to muscle atrophy, paralysis, and death due to respiratory failure. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) with a length of 19 to 25 nucleotides, participating in the regulation of gene expression. Different studies have demonstrated that miRNAs deregulation is critical for the onset of a considerable number of neurodegenerative diseases, including ALS. Some studies have underlined how miRNAs are deregulated in ALS patients and for this reason, design therapies are used to correct the aberrant expression of miRNAs. With this rationale, delivery systems can be designed to target specific miRNAs. Specifically, these systems can be derived from viral vectors (viral systems) or synthetic or natural materials, including exosomes, lipids, and polymers. Between many materials used for non-viral vectors production, the two-dimensional graphene and its derivatives represent a good alternative for efficiently delivering nucleic acids. The large surface-to-volume ratio and ability to penetrate cell membranes are among the advantages of graphene. This review focuses on the specific pathogenesis of miRNAs in ALS and on graphene delivery systems designed for gene delivery to create a primer for future studies in the field.
肌萎缩侧索硬化症(ALS)的特征是运动神经元的退化和死亡。这种神经退行性疾病会导致肌肉萎缩、瘫痪,并因呼吸衰竭而死亡。微小RNA(miRNA)是长度为19至25个核苷酸的小型非编码核糖核酸(RNA),参与基因表达的调控。不同的研究表明,miRNA失调对于包括ALS在内的许多神经退行性疾病的发病至关重要。一些研究强调了ALS患者中miRNA是如何失调的,因此,设计疗法用于纠正miRNA的异常表达。基于这一原理,可以设计递送系统来靶向特定的miRNA。具体而言,这些系统可以源自病毒载体(病毒系统)或合成或天然材料,包括外泌体、脂质和聚合物。在用于生产非病毒载体的许多材料中,二维石墨烯及其衍生物是有效递送核酸的良好替代品。石墨烯的优势包括大的表面积与体积比以及穿透细胞膜的能力。本综述重点关注ALS中miRNA的具体发病机制以及为基因递送而设计的石墨烯递送系统,为该领域的未来研究创建一个入门指南。