Iranpanah Amin, Kooshki Leila, Moradi Seyed Zachariah, Saso Luciano, Fakhri Sajad, Khan Haroon
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
USERN Office, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran.
Pharmaceutics. 2023 Mar 21;15(3):1006. doi: 10.3390/pharmaceutics15031006.
As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological diseases are important causes of disability and mortality. Neurological diseases affect millions of people worldwide. Recent studies have indicated that apoptosis, inflammation, and oxidative stress are the main players of NDDs and have critical roles in neurodegenerative processes. During the aforementioned inflammatory/apoptotic/oxidative stress procedures, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role. Considering the functional and structural aspects of the blood-brain barrier, drug delivery to the central nervous system is relatively challenging. Exosomes are nanoscale membrane-bound carriers that can be secreted by cells and carry several cargoes, including proteins, nucleic acids, lipids, and metabolites. Exosomes significantly take part in the intercellular communications due to their specific features including low immunogenicity, flexibility, and great tissue/cell penetration capabilities. Due to their ability to cross the blood-brain barrier, these nano-sized structures have been introduced as proper vehicles for central nervous system drug delivery by multiple studies. In the present systematic review, we highlight the potential therapeutic effects of exosomes in the context of NDDs and neurological diseases by targeting the PI3K/Akt/mTOR signaling pathway.
作为与快速增长的老龄化人口相关的主要公共卫生问题,神经退行性疾病(NDDs)和神经系统疾病是导致残疾和死亡的重要原因。神经系统疾病影响着全球数百万人。最近的研究表明,细胞凋亡、炎症和氧化应激是神经退行性疾病的主要因素,并且在神经退行性过程中起着关键作用。在上述炎症/细胞凋亡/氧化应激过程中,磷酸肌醇3激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素哺乳动物靶蛋白(mTOR)信号通路起着至关重要的作用。考虑到血脑屏障的功能和结构方面,向中枢神经系统给药相对具有挑战性。外泌体是纳米级的膜结合载体,可由细胞分泌并携带多种物质,包括蛋白质、核酸、脂质和代谢产物。外泌体因其低免疫原性、灵活性和强大的组织/细胞穿透能力等特定特性,在细胞间通讯中发挥着重要作用。由于它们能够穿过血脑屏障,多项研究已将这些纳米结构作为中枢神经系统药物递送的合适载体。在本系统评价中,我们通过靶向PI3K/Akt/mTOR信号通路,突出了外泌体在神经退行性疾病和神经系统疾病背景下的潜在治疗作用。