Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain and Cognition, Tarbiat Modares University, Tehran, Iran; Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Pharmacol Res. 2021 May;167:105441. doi: 10.1016/j.phrs.2021.105441. Epub 2021 Jan 24.
As described by Jean Martin Charcot in 1868, multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) which leads to permanent disability in patients. Following CNS insults, astrocytes and microglial cells undergo changes, which lead to scar formation in the site of injury. Owning to the pathophysiology of MS lesions, changes in both cellular and extracellular matrix (ECM) components occur over the progression of disease. In spite of advances in therapeutic approaches, drug delivery to MS lesions appears of great interest with big challenges and limitations. Targeting with peptides is a novel promising approach in the field of drug delivery. Recently peptides have been used for active targeting of different pathological disorders in which specific peptides make targeted accumulation of cargos to enhance local drug concentration at the pathological area, lead to increased therapeutic efficacy and decreased side effects. However, specific approaches for targeting the lesion in MS are still lacking. In this review, we discuss the changes of the ECM components as well as the cellular characteristics of demyelinated lesions and emphasis on opportunities for peptide based targeted drug delivery to highlight the possibility of such approaches for neurodegenerative disease with specific focus on MS.
正如让·马丁·夏科(Jean Martin Charcot)在 1868 年所描述的,多发性硬化症(MS)是一种中枢神经系统(CNS)的炎症、脱髓鞘和神经退行性疾病,可导致患者永久残疾。在中枢神经系统受到损伤后,星形胶质细胞和小胶质细胞发生变化,导致损伤部位形成瘢痕。由于 MS 病变的病理生理学,在疾病进展过程中,细胞和细胞外基质(ECM)成分都会发生变化。尽管在治疗方法上取得了进展,但药物递送至 MS 病变部位仍然具有很大的挑战性和局限性。肽靶向是药物递送领域的一种新的有前途的方法。最近,肽已被用于针对不同病理疾病的主动靶向,其中特定的肽使载体靶向积累,以增加病变部位的局部药物浓度,提高治疗效果并降低副作用。然而,针对 MS 病变的特定靶向方法仍然缺乏。在这篇综述中,我们讨论了 ECM 成分的变化以及脱髓鞘病变的细胞特征,并强调了基于肽的靶向药物递送的机会,以突出此类方法在神经退行性疾病中的可能性,特别是针对 MS。