Ahmed Sakeel, Pande Abhay H, Sharma Shyam Sunder
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
Exp Neurol. 2022 Jul;353:114051. doi: 10.1016/j.expneurol.2022.114051. Epub 2022 Mar 18.
The prevalence and burden of CNS disorders are increasing significantly due to the increase in life span and population. The contemporary need in CNS drug discovery is to develop the therapy that can halt the disease progression (disease-modifying therapy). While developing such CNS therapies, the major bottleneck is the blood-brain barrier (BBB) impermeability of drugs that influences the development of effective therapies to treat various CNS disorders. Since the influential innovation of insulin to treat diabetic patients in the 1920s, a lot of attention has been given for producing therapeutic proteins and peptides as remedies for several diseases, including neurological disorders. Recently, researchers have explored therapeutic potential of apolipoprotein E (ApoE)-mimetic peptides in the same context. ApoE is the major apolipoprotein produced in the brain by the astrocytes and plays a significant role in the formation of synapses, myelination, and neuronal proliferation. ApoE can be a potential candidate for treating CNS disorders. However, the large size of the ApoE leads to the BBB impermeability that restricts its use in native form. This problem can be overcome by developing small ApoE-mimetic peptides with good BBB permeability and similar biological function as native ApoE. Various ApoE-mimetic peptides have been developed and investigated in different CNS disorders. This review provide insights into the latest development of ApoE and its mimetic peptides in CNS disorders, along with their beneficial outcomes.
由于寿命延长和人口增长,中枢神经系统疾病的患病率和负担正在显著增加。中枢神经系统药物研发的当代需求是开发能够阻止疾病进展的疗法(疾病修饰疗法)。在开发此类中枢神经系统疗法时,主要瓶颈是药物的血脑屏障(BBB)不渗透性,这影响了治疗各种中枢神经系统疾病的有效疗法的开发。自20世纪20年代胰岛素用于治疗糖尿病患者这一具有影响力的创新以来,人们对生产治疗性蛋白质和肽作为多种疾病(包括神经系统疾病)的治疗方法给予了大量关注。最近,研究人员在相同背景下探索了载脂蛋白E(ApoE)模拟肽的治疗潜力。ApoE是星形胶质细胞在大脑中产生的主要载脂蛋白,在突触形成、髓鞘形成和神经元增殖中起重要作用。ApoE可能是治疗中枢神经系统疾病的潜在候选物。然而,ApoE的大尺寸导致血脑屏障不渗透性,限制了其天然形式的使用。通过开发具有良好血脑屏障通透性且与天然ApoE具有相似生物学功能的小ApoE模拟肽,可以克服这个问题。已经开发了各种ApoE模拟肽并在不同的中枢神经系统疾病中进行了研究。这篇综述深入探讨了ApoE及其模拟肽在中枢神经系统疾病中的最新进展及其有益成果。