ArticleProceedings of the National Academy of Sciences of the United States of America2021
PACAP is a pathogen-inducible resident antimicrobial neuropeptide affording rapid and contextual molecular host defense of the brain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease.Frontiers in immunology · 2024Pooled it
- Infection control in the brain and the eye.Acta ophthalmologica · 2026Review
- Emerging host-directed strategies for overcoming drug resistance and immune evasion in Staphylococcus aureus infections.Journal of advanced research · 2026Review
- Virulence Phenotypes Differentiate Persistent vs. Resolving Isolates of HumanAntibiotics (Basel, Switzerland) · 2026Article
- From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biguanide-functionalized peptide mimics effectively combat drug-resistant ESKAPE pathogens and meningitis.Nature communications · 2025Article
- Neuro-immuno-endocrinology of the skin: how environment regulates body homeostasis.Nature reviews. Endocrinology · 2025Review
- Neuropeptide-mediated activation of astrocytes improves stress resilience in mice by modulating cortical neural synapses.Acta pharmacologica Sinica · 2025Article
- The neuropeptidomes of the sea cucumbers Stichopus cf. horrens and Holothuria scabra.Scientific reports · 2025Article
- Novel technologies uncover novel 'anti'-microbial peptides inPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection.Nature communications · 2024Article
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.Current protein & peptide science · 2024Review
- The effect of PACAP administration on LPS-induced cytokine expression in the Atlantic salmon SHK-1 cell line.Fish and shellfish immunology reports · 2023Article
- PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.Acta pharmacologica Sinica · 2023Article
- A marmoset brain cell census reveals regional specialization of cellular identities.Science advances · 2023Article
- Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.Journal of nanobiotechnology · 2023Article
- The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease.Pharmaceutics · 2023Review
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13 authors at 7 institutions in 1 country.
Funding
Abstract
Defense of the central nervous system (CNS) against infection must be accomplished without generation of potentially injurious immune cell-mediated or off-target inflammation which could impair key functions. As the CNS is an immune-privileged compartment, inducible innate defense mechanisms endogenous to the CNS likely play an essential role in this regard. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known to regulate neurodevelopment, emotion, and certain stress responses. While PACAP is known to interact with the immune system, its significance in direct defense of brain or other tissues is not established. Here, we show that our machine-learning classifier can screen for immune activity in neuropeptides, and correctly identified PACAP as an antimicrobial neuropeptide in agreement with previous experimental work. Furthermore, synchrotron X-ray scattering, antimicrobial assays, and mechanistic fingerprinting provided precise insights into how PACAP exerts antimicrobial activities vs. pathogens via multiple and synergistic mechanisms, including dysregulation of membrane integrity and energetics and activation of cell death pathways. Importantly, resident PACAP is selectively induced up to 50-fold in the brain in mouse models of
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.