Hasina Zinnat, Wang Nicole, Wang Chi Chiu
Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
School of Veterinary Medicine, Glasgow University, Glasgow, United Kingdom.
Front Cell Dev Biol. 2022 May 23;10:877711. doi: 10.3389/fcell.2022.877711. eCollection 2022.
Individuals with Down syndrome (DS) suffer from developmental delay, intellectual disability, and an early-onset of neurodegeneration, Alzheimer's-like disease, or precocious dementia due to an extra chromosome 21. Studying the changes in anatomical, cellular, and molecular levels involved may help to understand the pathogenesis and develop target treatments, not just medical, but also surgical, cell and gene therapy, etc., for individuals with DS. Here we aim to identify key neurodevelopmental manifestations, locate knowledge gaps, and try to build molecular networks to better understand the mechanisms and clinical importance. We summarize current information about the neuropathology and neurodegeneration of the brain from conception to adulthood of foetuses and individuals with DS at anatomical, cellular, and molecular levels in humans. Understanding the alterations and characteristics of developing Down syndrome will help target treatment to improve the clinical outcomes. Early targeted intervention/therapy for the manifestations associated with DS in either the prenatal or postnatal period may be useful to rescue the neuropathology and neurodegeneration in DS.
唐氏综合征（DS）患者由于多了一条21号染色体，会出现发育迟缓、智力残疾以及神经退行性变、阿尔茨海默病样疾病或早熟性痴呆的早发症状。研究相关的解剖学、细胞和分子水平的变化，可能有助于理解发病机制，并为唐氏综合征患者开发靶向治疗方法，不仅包括医学治疗，还包括手术、细胞和基因治疗等。在这里，我们旨在识别关键的神经发育表现，找出知识空白，并尝试构建分子网络，以更好地理解其机制和临床重要性。我们总结了目前关于人类胎儿和唐氏综合征患者从受孕到成年期大脑神经病理学和神经退行性变在解剖学、细胞和分子水平上的信息。了解唐氏综合征发育过程中的改变和特征将有助于靶向治疗以改善临床结果。在产前或产后对与唐氏综合征相关的表现进行早期靶向干预/治疗，可能有助于挽救唐氏综合征患者的神经病理学和神经退行性变。
