组蛋白
细胞外
细胞生物学
生物
神经炎症
先天免疫系统
中性粒细胞胞外陷阱
愤怒(情绪)
炎症体
小胶质细胞
HMGB1
免疫系统
神经科学
免疫学
炎症
生物化学
基因
作者
Christy M. Richards,Seamus A. McRae,Athena L. Ranger,Andis Klegeris
出处
期刊:Reviews in The Neurosciences
[De Gruyter]
日期:2022-11-11
卷期号:34 (5): 533-558
被引量:13
标识
DOI:10.1515/revneuro-2022-0091
摘要
Abstract The four core histones H2A, H2B, H3, H4, and the linker histone H1 primarily bind DNA and regulate gene expression within the nucleus. Evidence collected mainly from the peripheral tissues illustrates that histones can be released into the extracellular space by activated or damaged cells. In this article, we first summarize the innate immune-modulatory properties of extracellular histones and histone-containing complexes, such as nucleosomes, and neutrophil extracellular traps (NETs), described in peripheral tissues. There, histones act as damage-associated molecular patterns (DAMPs), which are a class of endogenous molecules that trigger immune responses by interacting directly with the cellular membranes and activating pattern recognition receptors (PRRs), such as toll-like receptors (TLR) 2, 4, 9 and the receptor for advanced glycation end-products (RAGE). We then focus on the available evidence implicating extracellular histones as DAMPs of the central nervous system (CNS). It is becoming evident that histones are present in the brain parenchyma after crossing the blood-brain barrier (BBB) or being released by several types of brain cells, including neurons, microglia, and astrocytes. However, studies on the DAMP-like effects of histones on CNS cells are limited. For example, TLR4 is the only known molecular target of CNS extracellular histones and their interactions with other PRRs expressed by brain cells have not been observed. Nevertheless, extracellular histones are implicated in the pathogenesis of a variety of neurological disorders characterized by sterile neuroinflammation; therefore, detailed studies on the role these proteins and their complexes play in these pathologies could identify novel therapeutic targets.
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