Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
Dev Neurobiol. 2019 Jul;79(7):639-655. doi: 10.1002/dneu.22712. Epub 2019 Aug 6.
Down syndrome (DS) is a multisystem disorder affecting 1 in 800 births worldwide. Advancing technology, medical treatment, and social intervention have dramatically increased life expectancy, yet there are many etiologies of this disorder that are in need of further research. The advent of the ability to capture extracellular vesicles (EVs) in blood from specific cell types allows for the investigation of novel intracellular processes. Exosomes are one type of EVs that have demonstrated great potential in uncovering new biomarkers of neurodegeneration and disease, and also that appear to be intricately involved in the transsynaptic spread of pathogenic factors underlying Alzheimer's disease and other neurological diseases. Exosomes are nanosized vesicles, generated in endosomal multivesicular bodies (MVBs) and secreted by most cells in the body. Since exosomes are important mediators of intercellular communication and genetic exchange, they have emerged as a major research focus and have revealed novel biological sequelae involved in conditions afflicting the DS population. This review summarizes current knowledge on exosome biology in individuals with DS, both early in life and in aging individuals. Collectively these studies have demonstrated that complex multicellular processes underlying DS etiologies may include abnormal formation and secretion of extracellular vesicles such as exosomes.
唐氏综合征(DS)是一种多系统疾病,全球每 800 例出生中就有 1 例。先进的技术、医疗和社会干预措施极大地延长了患者的预期寿命,但这种疾病的许多病因仍需要进一步研究。能够从特定细胞类型的血液中捕获细胞外囊泡(EVs)的出现,为研究新的细胞内过程提供了可能。外泌体是 EVs 的一种类型,它们在揭示神经退行性疾病和疾病的新型生物标志物方面显示出巨大的潜力,并且似乎与阿尔茨海默病和其他神经退行性疾病的潜在致病性因素的突触间传播密切相关。外泌体是纳米大小的囊泡,在核内体多泡体(MVB)中产生,并由体内大多数细胞分泌。由于外泌体是细胞间通讯和遗传交换的重要介质,因此它们已成为主要的研究焦点,并揭示了与影响 DS 人群的疾病相关的新的生物学后果。本文综述了 DS 个体中外泌体生物学的最新知识,包括生命早期和衰老个体中的相关知识。这些研究表明,DS 病因的复杂多细胞过程可能包括细胞外囊泡(如外泌体)的异常形成和分泌。