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细胞外囊泡在神经退行性、精神和其他神经疾病中的作用:对机制、生物标志物潜力和治疗意义的认识。

Extracellular vesicles in neurodegenerative, mental, and other neurological disorders: Perspectives into mechanisms, biomarker potential, and therapeutic implications.

机构信息

Department of Morphology and Genetics, Universidade Federal de São Paulo, Brazil; Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, Brazil.

Center for Genomic Medicine, Massachusetts General Hospital, United States; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, United States.

出版信息

Curr Top Membr. 2024;94:299-336. doi: 10.1016/bs.ctm.2024.06.002. Epub 2024 Aug 31.

Abstract

Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.

摘要

细胞外囊泡 (EVs) 由包括组成神经系统组织的细胞在内的大多数人类细胞产生、分泌和靶向。EVs 携带几种类型的生物分子,如脂质、蛋白质和 microRNA,并在生理和病理过程中充当信号剂。在本章中,我们将重点介绍由脑细胞(特别是神经元和神经胶质细胞)分泌的 EV 及其 cargo,以及这些方面在病理条件下如何受到影响。本章涵盖了神经退行性疾病,包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症,以及几种精神疾病,即精神分裂症、自闭症谱系障碍和重度抑郁症。本章还涉及其他类型的神经功能障碍,如癫痫和创伤性脑损伤。EVs 可以穿过血脑屏障,因此脑 EVs 可能在外周更容易获得的组织中检测到,例如循环血液。因此,EV 组成和内容的改变可以为这些疾病的分子病因提供有价值的线索,并作为疾病流行、进展和治疗的生物标志物。EVs 还可以用于将药物和生物分子递送到脑组织中,被认为是治疗神经疾病的有前途的药物递送剂。因此,尽管这一研究领域仍处于早期发展阶段,但它在进一步阐明和治疗神经疾病方面具有巨大潜力。

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