Paseban Tahere, Alavi Mohaddeseh Sadat, Etemad Leila, Roohbakhsh Ali
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
Expert Opin Ther Targets. 2023 Jul-Dec;27(7):531-552. doi: 10.1080/14728222.2023.2235718. Epub 2023 Jul 17.
Cholesterol homeostasis is critical for normal brain function. It is tightly controlled by various biological elements. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that effluxes cholesterol from cells, particularly astrocytes, into the extracellular space. The recent studies pertaining to ABCA1's role in CNS disorders were included in this study.
In this comprehensive literature review, preclinical and human studies showed that ABCA1 has a significant role in the following diseases or disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, neuropathy, anxiety, depression, psychosis, epilepsy, stroke, and brain ischemia and trauma.
ABCA1 via modulating normal and aberrant brain functions such as apoptosis, phagocytosis, BBB leakage, neuroinflammation, amyloid β efflux, myelination, synaptogenesis, neurite outgrowth, and neurotransmission promotes beneficial effects in aforementioned diseases. ABCA1 is a key molecule in the CNS. By boosting its expression or function, some CNS disorders may be resolved. In preclinical studies, liver X receptor agonists have shown promise in treating CNS disorders via ABCA1 and apoE enhancement.
胆固醇稳态对正常脑功能至关重要。它受到多种生物因素的严格调控。ATP结合盒转运蛋白A1(ABCA1)是一种膜转运蛋白,可将胆固醇从细胞(尤其是星形胶质细胞)排出到细胞外空间。本研究纳入了近期有关ABCA1在中枢神经系统疾病中作用的研究。
在这篇全面的文献综述中,临床前和人体研究表明ABCA1在以下疾病或病症中发挥重要作用:阿尔茨海默病、帕金森病、亨廷顿病、多发性硬化症、神经病变、焦虑症、抑郁症、精神病、癫痫、中风以及脑缺血和创伤。
ABCA1通过调节诸如细胞凋亡、吞噬作用、血脑屏障渗漏、神经炎症、淀粉样β蛋白外流、髓鞘形成、突触发生、神经突生长和神经传递等正常和异常脑功能,对上述疾病产生有益影响。ABCA1是中枢神经系统中的关键分子。通过提高其表达或功能,一些中枢神经系统疾病可能得到解决。在临床前研究中,肝脏X受体激动剂已显示出通过增强ABCA1和载脂蛋白E来治疗中枢神经系统疾病的前景。