Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression

	Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression
	Chen, X; Deng, SX; Wang, WC; Castiglione, S; Duan, ZL; Luo, L; Cianci, F; Zhang, XX; Xu, JL; Li, H; Zhao, JZ; Kamau, PM; Zhang, ZY; Mwangi, J; Li, JL; Shu, YS; Hu, XT; Mazzanti, M; Lai, R
	2022
发表期刊	MOLECULAR PSYCHIATRY
ISSN	1359-4184
摘要	As a prime mover in Alzheimer's disease (AD), microglial activation requires membrane translocation, integration, and activation of the metamorphic protein chloride intracellular channel 1 (CLIC1), which is primarily cytoplasmic under physiological conditions. However, the formation and activation mechanisms of functional CLIC1 are unknown. Here, we found that the human antimicrobial peptide (AMP) LL-37 promoted CLIC1 membrane translocation and integration. It also activates CLIC1 to cause microglial hyperactivation, neuroinflammation, and excitotoxicity. In mouse and monkey models, LL-37 caused significant pathological phenotypes linked to AD, including elevated amyloid-beta, increased neurofibrillary tangles, enhanced neuronal death and brain atrophy, enlargement of lateral ventricles, and impairment of synaptic plasticity and cognition, while Clic1 knockout and blockade of LL-37-CLIC1 interactions inhibited these phenotypes. Given AD's association with infection and that overloading AMP may exacerbate AD, this study suggests that LL-37, which is up-regulated upon infection, may be a driving force behind AD by acting as an endogenous agonist of CLIC1.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13218
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Chen, X,Deng, SX,Wang, WC,et al. Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression[J]. MOLECULAR PSYCHIATRY,2022.
APA	Chen, X.,Deng, SX.,Wang, WC.,Castiglione, S.,Duan, ZL.,...&Lai, R.(2022).Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression.MOLECULAR PSYCHIATRY.
MLA	Chen, X,et al."Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression".MOLECULAR PSYCHIATRY (2022).

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