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操作脉络丛上皮细胞的实验方法。

Experimental approaches for manipulating choroid plexus epithelial cells.

机构信息

Department of Pathology, Boston Children's Hospital, Boston, MA, 02115, USA.

出版信息

Fluids Barriers CNS. 2022 May 26;19(1):36. doi: 10.1186/s12987-022-00330-2.

DOI:10.1186/s12987-022-00330-2
PMID:35619113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9134666/
Abstract

Choroid plexus (ChP) epithelial cells are crucial for the function of the blood-cerebrospinal fluid barrier (BCSFB) in the developing and mature brain. The ChP is considered the primary source and regulator of CSF, secreting many important factors that nourish the brain. It also performs CSF clearance functions including removing Amyloid beta and potassium. As such, the ChP is a promising target for gene and drug therapy for neurodevelopmental and neurological disorders in the central nervous system (CNS). This review describes the current successful and emerging experimental approaches for targeting ChP epithelial cells. We highlight methodological strategies to specifically target these cells for gain or loss of function in vivo. We cover both genetic models and viral gene delivery systems. Additionally, several lines of reporters to access the ChP epithelia are reviewed. Finally, we discuss exciting new approaches, such as chemical activation and transplantation of engineered ChP epithelial cells. We elaborate on fundamental functions of the ChP in secretion and clearance and outline experimental approaches paving the way to clinical applications.

摘要

脉络丛(ChP)上皮细胞对于发育中和成熟脑中的血脑屏障(BCSFB)的功能至关重要。脉络丛被认为是脑脊液(CSF)的主要来源和调节者,分泌许多滋养大脑的重要因子。它还具有脑脊液清除功能,包括清除β淀粉样蛋白和钾。因此,脉络丛是中枢神经系统(CNS)中神经发育和神经病变的基因和药物治疗的有前途的靶点。本综述描述了针对脉络丛上皮细胞的当前成功和新兴实验方法。我们强调了用于在体内获得或丧失功能的特定靶向这些细胞的方法策略。我们涵盖了遗传模型和病毒基因传递系统。此外,还回顾了几种用于访问脉络丛上皮的报告基因。最后,我们讨论了令人兴奋的新方法,如化学激活和工程化脉络丛上皮细胞的移植。我们详细阐述了脉络丛在分泌和清除方面的基本功能,并概述了为临床应用铺平道路的实验方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/a3b2b73fba56/12987_2022_330_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/8fc0e7e80c72/12987_2022_330_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/92127a0acd78/12987_2022_330_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/a3b2b73fba56/12987_2022_330_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/8fc0e7e80c72/12987_2022_330_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/92127a0acd78/12987_2022_330_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdf/9134666/a3b2b73fba56/12987_2022_330_Fig3_HTML.jpg

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AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset.在小鼠和狨猴静脉注射后具有全脑转基因表达且肝脏靶向性降低的腺相关病毒衣壳变体。
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