小胶质细胞异质性在突触可塑性和脑部疾病中的作用:测序能否发现新的治疗靶点?

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Yi You , Zhong Chen , Wei-Wei Hu
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引用次数: 0

摘要

小胶质细胞在与神经元突触相互作用和调节突触可塑性方面发挥着至关重要的作用。这一功能在出生后的发育过程中尤为重要,因为小胶质细胞负责清除过多的突触,以防止神经发育障碍。小胶质细胞突触功能失调已在各种病理情况中得到充分证实,尤其是阿尔茨海默病和多发性硬化症。最近,RNA 测序技术的应用为破译小胶质细胞的空间和时间异质性提供了一种强大而无偏见的方法。通过识别具有不同基因表达谱的小胶质细胞,研究人员定义了与特定病理状态相关的多个小胶质细胞亚群,包括疾病相关小胶质细胞、干扰素反应性小胶质细胞、增殖小胶质细胞和多发性硬化症中的炎性小胶质细胞等。然而,这些不同亚群的功能作用仍未得到充分描述。本综述旨在通过最近的测序研究和功能研究,完善我们目前对异质性小胶质细胞在调节突触可塑性方面的潜在作用及其对各种脑部疾病的影响的认识。这些知识有助于确定致病生物标志物和潜在的致病因素,为发现新的药物靶点提供新的启示。基于测序的数据挖掘领域正朝着多组学方法发展。随着用于精确调控小胶质细胞的病毒工具的进步和类脑器官模型的开发,我们有望阐明通过测序分析检测到的小胶质细胞亚群的功能作用,最终确定有价值的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of microglia heterogeneity in synaptic plasticity and brain disorders: Will sequencing shed light on the discovery of new therapeutic targets?

Microglia play a crucial role in interacting with neuronal synapses and modulating synaptic plasticity. This function is particularly significant during postnatal development, as microglia are responsible for removing excessive synapses to prevent neurodevelopmental deficits. Dysregulation of microglial synaptic function has been well-documented in various pathological conditions, notably Alzheimer's disease and multiple sclerosis. The recent application of RNA sequencing has provided a powerful and unbiased means to decipher spatial and temporal microglial heterogeneity. By identifying microglia with varying gene expression profiles, researchers have defined multiple subgroups of microglia associated with specific pathological states, including disease-associated microglia, interferon-responsive microglia, proliferating microglia, and inflamed microglia in multiple sclerosis, among others. However, the functional roles of these distinct subgroups remain inadequately characterized. This review aims to refine our current understanding of the potential roles of heterogeneous microglia in regulating synaptic plasticity and their implications for various brain disorders, drawing from recent sequencing research and functional studies. This knowledge may aid in the identification of pathogenetic biomarkers and potential factors contributing to pathogenesis, shedding new light on the discovery of novel drug targets. The field of sequencing-based data mining is evolving toward a multi-omics approach. With advances in viral tools for precise microglial regulation and the development of brain organoid models, we are poised to elucidate the functional roles of microglial subgroups detected through sequencing analysis, ultimately identifying valuable therapeutic targets.

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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
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