CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(2), P. 1565 - 1644

Published: Dec. 1, 2022

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons as well other cell types, such motor neuroendocrine cells. CGRP acts via at least G protein-coupled receptors that form unusual complexes receptor activity-modifying proteins. These AMY

Language: Английский

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CGRP sensory neurons promote tissue healing via neutrophils and macrophages

Nature, Journal Year: 2024, Volume and Issue: 628(8008), P. 604 - 611

Published: March 27, 2024

Abstract The immune system has a critical role in orchestrating tissue healing. As result, regenerative strategies that control components have proved effective 1,2 . This is particularly relevant when dysregulation results from conditions such as diabetes or advanced age impairs healing following injury 2,3 Nociceptive sensory neurons crucial immunoregulators and exert both protective harmful effects depending on the context 4–12 However, how neuro–immune interactions affect repair regeneration acute unclear. Here we show ablation of Na V 1.8 nociceptor skin wound muscle after injury. Nociceptor endings grow into injured tissues signal to cells through neuropeptide calcitonin gene-related peptide (CGRP) during process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) neutrophils, monocytes macrophages inhibit recruitment, accelerate death, enhance efferocytosis polarize towards pro-repair phenotype. neutrophils are mediated thrombospondin-1 release its subsequent autocrine and/or paracrine effects. In mice without nociceptors diabetic with peripheral neuropathies, delivery an engineered version accelerated promoted regeneration. Harnessing potential treat non-healing which dysregulated impair

Language: Английский

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Stress-sensitive neural circuits change the gut microbiome via duodenal glands

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5393 - 5412.e30

Published: Aug. 8, 2024

Negative psychological states impact immunity by altering the gut microbiome. However, relationship between brain and microbiome composition remains unclear. We show that Brunner's glands in duodenum couple stress-sensitive circuits to bacterial homeostasis. mediated enrichment of Lactobacillus species response vagus nerve stimulation. Cell-specific ablation markedly suppressed Lactobacilli counts heightened vulnerability infection. In forebrain, we mapped a vagally mediated, polysynaptic circuit connecting central nucleus amygdala glands. Chronic stress activity phenocopied effects gland lesions. Conversely, excitation either or parasympathetic vagal neurons activated reversed on immunity. The findings revealed tractable brain-body mechanism linking host defense.

Language: Английский

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A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut

Science, Journal Year: 2024, Volume and Issue: 385(6708)

Published: Aug. 1, 2024

Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays molecularly defined neuron subsets immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, transcriptomics organs. Distinct immune perturbations followed activation: Nitrergic neurons regulated T helper 17 (T

Language: Английский

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Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity

Cell, Journal Year: 2024, Volume and Issue: 187(12), P. 2935 - 2951.e19

Published: May 20, 2024

Language: Английский

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Pathology of pain and its implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 8, 2024

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.

Language: Английский

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Neuroimmune Interactions in the Intestine

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 489 - 519

Published: June 28, 2024

Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role this cross talk for gut homeostasis modulation inflammatory infectious intestinal diseases. In review, we describe innervation by intrinsic extrinsic neurons then focus on bidirectional communication between immune cells. First, highlight contribution neuronal subtypes development colitis discuss different epithelial cell types that are regulated via release neuropeptides neurotransmitters. Next, review inflammation visceral hypersensitivity summarize how mediators induce peripheral central sensitization gut-innervating sensory neurons. Finally, outline importance cells microbiota survival function populations at during bacterial helminth infection.

Language: Английский

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Bi-directional communication between intrinsic enteric neurons and ILC2s inhibits host defense against helminth infection

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Nociceptive neurons promote gastric tumour progression via a CGRP–RAMP1 axis

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

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Boundaries and integration between microbiota, the nervous system, and immunity

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1712 - 1726

Published: Aug. 1, 2023

Language: Английский

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