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核受体与少突胶质前体细胞的分化。

Nuclear receptors and differentiation of oligodendrocyte precursor cells.

机构信息

Interdepartmental Center for Industrial Research in Health Sciences and Technologies, University of Bologna, Bologna, Italy.

Interdepartmental Center for Industrial Research in Health Sciences and Technologies, University of Bologna, Bologna, Italy.

出版信息

Vitam Horm. 2021;116:389-407. doi: 10.1016/bs.vh.2021.02.002. Epub 2021 Mar 9.

Abstract

Oligodendrocytes are the cells responsible for myelin formation during development and in adulthood, both for normal myelin turnover and myelin repair. These highly specialized cells derive from the oligodendrocyte precursor cells (OPCs), through a complex differentiation process involving genetic and epigenetic regulation mechanisms, which switch the phenotype from a migratory and replicative precursor to a mature post-mitotic cell. The process is regulated by a plethora of molecules, involving neurotransmitters, growth factors, hormones and other small molecules, and is mainly driven by nuclear receptors (NRs). NRs are transcription factors with heterogeneous ligand-dependent and independent actions which differ for the cell target, the responsive gene and the formation of NR homo- or heterodimers. This chapter highlights the role of NRs in regulating OPC differentiation, also in view of drug discovery strategies aimed at targeting pathological conditions which interfere with both developmental myelination and remyelination in adulthood.

摘要

少突胶质细胞是在发育过程中和成年期负责髓鞘形成的细胞,无论是正常的髓鞘更新还是髓鞘修复。这些高度特化的细胞来源于少突胶质前体细胞(OPC),通过一个涉及遗传和表观遗传调控机制的复杂分化过程,将表型从迁移和复制前体细胞转变为成熟的有丝分裂后细胞。这个过程受到大量分子的调节,包括神经递质、生长因子、激素和其他小分子,主要由核受体(NRs)驱动。NRs 是转录因子,具有异质的配体依赖性和非依赖性作用,因细胞靶标、应答基因和 NR 同源或异源二聚体的形成而不同。本章重点介绍了 NRs 在调节 OPC 分化中的作用,也考虑了旨在针对干扰发育性髓鞘形成和成年期髓鞘修复的病理状况的药物发现策略。

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