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抗菌肽在先天免疫、神经元功能和神经退行性变中的新兴作用。

Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration.

机构信息

Frontotemporal Dementia Research Center, RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

出版信息

Trends Neurosci. 2024 Nov;47(11):949-961. doi: 10.1016/j.tins.2024.09.001. Epub 2024 Oct 9.

Abstract

Antimicrobial peptides (AMPs), a collection of small proteins with important roles in classical innate immunity, have been extensively studied in multiple organisms, particularly in Drosophila melanogaster. Advances in CRISPR/Cas9 genome editing have allowed individual AMP functions to be dissected, revealing specific and selective roles in host defense. Recent findings have also revealed many unexpected contributions of endogenous AMPs to neuronal functions and neurodegenerative diseases, and have shed light on the intersections between innate immunity and neurobiology. We explore the intricate relationships between AMPs and sleep regulation, memory formation, as well as traumatic brain injury and several neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Understanding the diverse functions of AMPs opens new avenues for neuroinflammation and neurodegenerative disease research and potential therapeutic development.

摘要

抗菌肽(AMPs)是一类在经典先天免疫中具有重要作用的小分子蛋白质,在多种生物中得到了广泛研究,尤其是在黑腹果蝇(Drosophila melanogaster)中。CRISPR/Cas9 基因组编辑技术的进步使得人们能够剖析单个 AMP 的功能,揭示其在宿主防御中的特异性和选择性作用。最近的研究结果还揭示了内源性 AMP 对神经元功能和神经退行性疾病的许多意外贡献,并阐明了先天免疫和神经生物学之间的交叉点。我们探讨了 AMP 与睡眠调节、记忆形成以及创伤性脑损伤以及几种神经退行性疾病(如阿尔茨海默病(AD)、额颞叶痴呆(FTD)和帕金森病(PD))之间的复杂关系。理解 AMP 的多种功能为神经炎症和神经退行性疾病研究以及潜在的治疗开发开辟了新的途径。

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本文引用的文献

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Innate immune activation in neurodegenerative diseases.神经退行性疾病中的先天免疫激活。
Immunity. 2024 Apr 9;57(4):790-814. doi: 10.1016/j.immuni.2024.03.010.
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The amphipathic design in helical antimicrobial peptides.两亲性设计在螺旋抗菌肽中的应用。
ChemMedChem. 2024 Apr 2;19(7):e202300480. doi: 10.1002/cmdc.202300480. Epub 2024 Feb 26.
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Microglia: Activity-dependent regulators of neural circuits.小胶质细胞:神经回路的活性依赖性调节者。
Ann N Y Acad Sci. 2024 Mar;1533(1):38-50. doi: 10.1111/nyas.15105. Epub 2024 Jan 31.

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