ArticleMolecular psychiatry2022
Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression.
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Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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17citing papers in PubMed
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17 citing papers in PubMed, 22 citations in OpenAlex.
- Antimicrobial proteins regulating neuroinflammation.Annals of medicine · 2026Review
- β-Amyloid (Aβ) and Human Cathelicidin LL-37: Two Sides of the Same Coin?International journal of molecular sciences · 2026Review
- Repurposing of doxycycline as a novel therapeutic avenue for management of parkinson's disease.Inflammopharmacology · 2026Review
- Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.Translational neurodegeneration · 2026Review
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Outer membrane vesicle contributes to theMedComm · 2025Article
- An Integrated Whole-Process Repair System with Programmed Regulation of Healing Performance Facilitates Urethral Wound Restoration and Scarless Reconstruction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bronchial epithelial cell-derived extracellular vesicles drive inflammasome activation andFrontiers in immunology · 2025Article
- Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration.Trends in neurosciences · 2024Review
- Inflammatory aspects of Alzheimer's disease.Acta neuropathologica · 2024Review
- Dermaseptin B2 bioactive gene's potential for anticancer and anti-proliferative effect is linked to the regulation of the BAX/BBC3/AKT pathway.Medical oncology (Northwood, London, England) · 2024Article
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Article
- Peptide-based approaches to directly target alpha-synuclein in Parkinson's disease.Molecular neurodegeneration · 2023Review
- Identification and Characterization of RK22, a Novel Antimicrobial Peptide fromInternational journal of molecular sciences · 2023Article
- Intracellular chloride channel 1 and tumor.American journal of cancer research · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 3 countries.
Xue Chen *Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.ORCID http://orcid.org/0000-0002-6579-947X
Suixin Deng *Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute for Translational Brain Research, Fudan University, Shanghai, 200032, China.ORCID http://orcid.org/0000-0003-4795-2570
Wenchao Wang *Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.ORCID http://orcid.org/0000-0002-5021-8660
Stefania Castiglione *Department of Biosciences, University of Milano, Via Celoria 26, I-20133, Milano, Italy.ORCID http://orcid.org/0000-0002-5999-8368
Zilei Duan *Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.ORCID http://orcid.org/0000-0002-3262-9685
Lei LuoKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Francesca CianciDepartment of Biosciences, University of Milano, Via Celoria 26, I-20133, Milano, Italy.
Xiaoxue ZhangDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute for Translational Brain Research, Fudan University, Shanghai, 200032, China.
Jianglei XuKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Hao LiBeijing Tiantan Hospital and China National Clinical Research Center for Neurological Diseases, Capital Medical University, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100071, China.
Jizong ZhaoBeijing Tiantan Hospital and China National Clinical Research Center for Neurological Diseases, Capital Medical University, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100071, China.
Peter Muiruri KamauKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Zhiye ZhangKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
James MwangiKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Jiali LiKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Yousheng ShuDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute for Translational Brain Research, Fudan University, Shanghai, 200032, China. yousheng@fudan.edu.cn.ORCID http://orcid.org/0000-0002-2834-2876
Xintian HuKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China. xthu@mail.kiz.ac.cn.ORCID http://orcid.org/0000-0003-1216-4806
Michele MazzantiDepartment of Biosciences, University of Milano, Via Celoria 26, I-20133, Milano, Italy. michele.mazzanti@unimi.it.ORCID http://orcid.org/0000-0002-1819-3811
Ren LaiKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China. rlai@mail.kiz.ac.cn.ORCID http://orcid.org/0000-0002-3123-2336
Kunming Institute of Zoology · CNFudan University · CNUniversity of Milan · ITCapital Medical University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-β, 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.
Indexed as
Alzheimer DiseaseCathelicidinsChloride ChannelsAmyloid beta-PeptidesAnimalsHumansMiceMicrogliaAmyloid beta-PeptidesCathelicidinsChloride ChannelsCLIC1 protein, human
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