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用于理解阿尔茨海默病和其他神经疾病的死后人体突触体研究:综述

The Study of Postmortem Human Synaptosomes for Understanding Alzheimer's Disease and Other Neurological Disorders: A Review.

作者信息

Jhou Jia-Fong, Tai Hwan-Ching

机构信息

Department of Chemistry, National Taiwan University, Taipei, Taiwan.

出版信息

Neurol Ther. 2017 Jul;6(Suppl 1):57-68. doi: 10.1007/s40120-017-0070-z. Epub 2017 Jul 21.

Abstract

Synaptic dysfunction is thought to play important roles in the pathophysiology of many neurological diseases, including Alzheimer's disease, Parkinson's disease, and schizophrenia. Over the past few decades, there have been systematic efforts to collect postmortem brain tissues via autopsies, leading to the establishment of dozens of human brain banks around the world. From cryopreserved human brain tissues, it is possible to isolate detached-and-resealed synaptic terminals termed synaptosomes, which remain metabolically and enzymatically active. Synaptosomes have become important model systems for studying human synaptic functions, being much more accessible than ex vivo brain slices or primary neuronal cultures. Here we review recent advances in the establishment of human brain banks, the isolation of synaptosomes, their biological activities, and various analytical techniques for investigating their biochemical and ultrastructural properties. There are unique insights to be gained by directly examining human synaptosomes, which cannot be substituted by animal models. We will also discuss how human synaptosome research has contributed to better understanding of neurological disorders, especially Alzheimer's disease.

摘要

突触功能障碍被认为在包括阿尔茨海默病、帕金森病和精神分裂症在内的许多神经疾病的病理生理学中起重要作用。在过去几十年里,人们通过尸检系统地努力收集死后脑组织,从而在世界各地建立了数十个人脑库。从冷冻保存的人脑组织中,可以分离出称为突触体的分离并重新封闭的突触终末,它们在代谢和酶活性方面仍然活跃。突触体已成为研究人类突触功能的重要模型系统,比体外脑片或原代神经元培养更容易获得。在这里,我们综述了人脑库建立、突触体分离、其生物学活性以及用于研究其生化和超微结构特性的各种分析技术的最新进展。直接检查人类突触体可获得独特的见解,这是动物模型无法替代的。我们还将讨论人类突触体研究如何有助于更好地理解神经疾病,尤其是阿尔茨海默病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf02/5520816/9d9c283730d0/40120_2017_70_Fig1_HTML.jpg

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