Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México. Unidad de Posgrado, Ciudad Universitaria, Ciudad de México, Mexico.
Adv Protein Chem Struct Biol. 2021;123:133-162. doi: 10.1016/bs.apcsb.2020.09.002. Epub 2020 Dec 19.
Iron transport in the central nervous system (CNS) is a highly regulated process in which several important proteins participate to ensure this important metal reaches its sites of action. However, iron accumulation has been shown to be a common factor in different neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Multiple Sclerosis, and Sanfilippo syndrome. This review is divided into four parts. The first part describes brain iron transport in homeostasis, mentioning the main proteins involved, whereas the second part contrasts the consequences of iron dysregulation, elaborating on its role in the aforementioned neurodegenerative diseases. The third part details the functions of the main proteins involved in brain iron homeostasis and their role in neurodegeneration. In the fourth part, in order to highlight the importance of transport proteins, the focus is set on human serum transferrin, the main iron transport protein. This final part describes perspectives about the mechanisms and chemical properties of human transferrin for the development of potential targeted drug delivery systems across the blood-brain barrier (BBB) or enhancers for the treatment of neurological diseases.
铁在中枢神经系统（CNS）中的转运是一个高度调控的过程，其中有几种重要的蛋白质参与其中，以确保这种重要金属到达其作用部位。然而，铁的积累已被证明是多种神经退行性疾病（如阿尔茨海默病、帕金森病、亨廷顿病、多发性硬化症和 Sanfilippo 综合征）的共同因素。这篇综述分为四部分。第一部分描述了脑内铁转运在体内平衡中的作用，提到了主要涉及的蛋白质，而第二部分则对比了铁失调的后果，详细阐述了其在上述神经退行性疾病中的作用。第三部分详细介绍了脑内铁稳态相关的主要蛋白质的功能及其在神经退行性变中的作用。在第四部分，为了强调转运蛋白的重要性，重点介绍了人类血清转铁蛋白，这是主要的铁转运蛋白。这最后一部分描述了人类转铁蛋白的机制和化学性质的研究进展，以期开发针对血脑屏障（BBB）的潜在靶向药物递送系统或治疗神经退行性疾病的增强剂。
