Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA.
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
Expert Opin Drug Deliv. 2020 Mar;17(3):323-340. doi: 10.1080/17425247.2020.1727443. Epub 2020 Feb 14.
: Neurodegenerative diseases are those wherein the neurons in the brain or peripheral nervous system lose their function, eventually culminating in neuronal death. Aging acts as the predominant factor here due to the reduced protein turnover rate in aging cells. As neurotrophic factors possess imperative roles in protecting the neurons and restoring their functionality, design of different modalities to deliver them to the brain would significantly enhance the therapeutic benefits.: This review covers the various mechanisms of neurodegeneration, its molecular link with aging, different neurotrophic factor classes and their potentials, current treatment strategies, the challenges associated with the delivery of neurotrophic factors, administration routes, design of different delivery vehicle design, alternative modalities of delivery, and the clinical translational challenges of these strategies.: A deeper molecular level understanding about the complexity of neurodegeneration, discovery of potential biomarkers, which helps identifying the right targets, finding the accurate animal model completely recapitulating the human scenario, and a validated design of clinical trials would immensely help in overcoming the present challenges. The substantial developments in the field of gene therapy, usage of small molecules and peptide mimetics, combinatory approaches, etc. definitely give brighter hopes.
神经退行性疾病是指大脑或周围神经系统中的神经元丧失功能,最终导致神经元死亡的疾病。衰老在这里是主要因素,因为衰老细胞中的蛋白质周转率降低。由于神经营养因子在保护神经元和恢复其功能方面具有重要作用,因此设计不同的方式将其递送到大脑中会显著提高治疗效果。
这篇综述涵盖了神经退行性变的各种机制、其与衰老的分子联系、不同的神经营养因子类别及其潜力、当前的治疗策略、与神经营养因子传递相关的挑战、给药途径、不同传递载体设计、替代传递方式以及这些策略的临床转化挑战。
对神经退行性变复杂性有更深入的分子水平理解、发现潜在的生物标志物,有助于确定正确的靶点,找到完全模拟人类情况的精确动物模型,以及经过验证的临床试验设计,将极大地有助于克服当前的挑战。基因治疗领域的重大进展、小分子和肽模拟物的使用、联合方法等,确实带来了更光明的希望。