Emerging contributions of formyl peptide receptors to neurodegenerative diseases

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Lukas Busch ◽  
Stefan Vieten ◽  
Susan Brödel ◽  
Kristina Endres ◽  
Bernd Bufe
Keyword(s):  
Neurodegenerative Diseases ◽  
Inflammatory Responses ◽  
Central Element ◽  
Peptide Receptors ◽  
Lipoxin A4 ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Dependent Signal ◽  
Dependent Cell ◽  
Novel Therapeutic Strategies

Abstract Inflammation is a central element of many neurodegenerative diseases. Formyl peptide receptors (FPRs) can trigger several receptor-dependent signal transduction pathways that play a key role in neuroinflammation and neurodegeneration. They are chemotactic receptors that help to regulate pro- and anti-inflammatory responses in most mammals. FPRs are primarily expressed in the immune and nervous systems where they interact with a complex pattern of pathogen-derived and host-endogenous molecules. Mounting evidence points towards a contribution of FPRs – via neuropathological ligands such as Amyloid beta, and neuroprotective ligands such as Humanin, Lipoxin A4, and Annexin A1 – to multiple pathological aspects of neurodegenerative diseases. In this review, we aim to summarize the interplay of FPRs with neuropathological and neuroprotective ligands. Next, we depict their capability to trigger a number of ligand-dependent cell signaling pathways and their potential to interact with additional intracellular cofactors. Moreover, we highlight first studies, demonstrating that a pharmacological inhibition of FPRs helps to ameliorate neuroinflammation, which may pave the way towards novel therapeutic strategies.

scholarly journals The Role of Formyl Peptide Receptors in Permanent and Low-Grade Inflammation: Helicobacter pylori Infection as a Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3706
Author(s):  
Paola Cuomo ◽  
Marina Papaianni ◽  
Rosanna Capparelli ◽  
Chiara Medaglia
Keyword(s):  
Helicobacter Pylori ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Surface Pattern ◽  
Low Grade ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

Formyl peptide receptors (FPRs) are cell surface pattern recognition receptors (PRRs), belonging to the chemoattractant G protein-coupled receptors (GPCRs) family. They play a key role in the innate immune system, regulating both the initiation and the resolution of the inflammatory response. FPRs were originally identified as receptors with high binding affinity for bacteria or mitochondria N-formylated peptides. However, they can also bind a variety of structurally different ligands. Among FPRs, formyl peptide receptor-like 1 (FPRL1) is the most versatile, recognizing N-formyl peptides, non-formylated peptides, and synthetic molecules. In addition, according to the ligand nature, FPRL1 can mediate either pro- or anti-inflammatory responses. Hp(2-20), a Helicobacter pylori-derived, non-formylated peptide, is a potent FPRL1 agonist, participating in Helicobacter pylori-induced gastric inflammation, thus contributing to the related site or not-site specific diseases. The aim of this review is to provide insights into the role of FPRs in H. pylori-associated chronic inflammation, which suggests this receptor as potential target to mitigate both microbial and sterile inflammatory diseases.

scholarly journals What Formyl Peptide Receptors, if Any, Are Triggered by Compound 43 and Lipoxin A4?

2011 ◽  
Vol 74 (3) ◽  
pp. 227-234 ◽  
Author(s):  
H. Forsman ◽  
K. Önnheim ◽  
E. Andreasson ◽  
C. Dahlgren
Keyword(s):  
Peptide Receptors ◽  
Lipoxin A4 ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

scholarly journals The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation

2021 ◽  
Vol 15 ◽  
Author(s):  
Jiahui Zhu ◽  
Lingfei Li ◽  
Jiao Ding ◽  
Jinyu Huang ◽  
Anwen Shao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Neurological Diseases ◽  
Cell Types ◽  
Dual Function ◽  
Peptide Receptors ◽  
Regulatory Pathways ◽  
Formyl Peptide Receptors ◽  
Neurogenic Tumors ◽  
Formyl Peptide

Formyl peptide receptors (FPRs) are a group of G protein-coupled cell surface receptors that play important roles in host defense and inflammation. Owing to the ubiquitous expression of FPRs throughout different cell types and since they interact with structurally diverse chemotactic agonists, they have a dual function in inflammatory processes, depending on binding with different ligands so that accelerate or inhibit key intracellular kinase-based regulatory pathways. Neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, neurogenic tumors and cerebrovascular diseases. From recent studies, it is clear that FPRs are important biomarkers for neurological diseases as they regulate inflammatory responses by monitoring glial activation, accelerating neural differentiation, regulating angiogenesis, and controlling blood brain barrier (BBB) permeability, thereby affecting neurological disease progression. Given the complex mechanisms of neurological diseases and the difficulty of healing, we are eager to find new and effective therapeutic targets. Here, we review recent research about various mechanisms of the effects generated after FPR binding to different ligands, role of FPRs in neuroinflammation as well as the development and prognosis of neurological diseases. We summarize that the FPR family has dual inflammatory functional properties in central nervous system. Emphasizing that FPR2 acts as a key molecule that mediates the active resolution of inflammation, which binds with corresponding receptors to reduce the expression and activation of pro-inflammatory composition, govern the transport of immune cells to inflammatory tissues, and restore the integrity of the BBB. Concurrently, FPR1 is essentially related to angiogenesis, cell proliferation and neurogenesis. Thus, treatment with FPRs-modulation may be effective for neurological diseases.

The Role of Formyl Peptide Receptors in Microbial Infection and Inflammation

2003 ◽  
Vol 2 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Yingying Le ◽  
Ronghua Sun ◽  
Guoguang Ying ◽  
Pablo Iribarren ◽  
Ji Wang
Keyword(s):  
Microbial Infection ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Infection And Inflammation

scholarly journals G-protein–coupled formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis

2019 ◽  
Vol 30 (3) ◽  
pp. 346-356 ◽  
Author(s):  
Xi Wen ◽  
Xuehua Xu ◽  
Wenxiang Sun ◽  
Keqiang Chen ◽  
Miao Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
G Protein Coupled Receptors ◽  
Peptide Receptors ◽  
Tyrosine Kinase Signaling ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
G Protein Coupled

A dogma of innate immunity is that neutrophils use G-protein–coupled receptors (GPCRs) for chemoattractant to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work showed that G-protein–coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2–/–) are defective in the phagocytosis of Escherichia coli and the chemoattractant N-formyl-Met-Leu-Phe (fMLP)-coated beads. fMLP immobilized onto the surface of a bead interacts with FPRs, which trigger a Ca2+response and induce actin polymerization to form a phagocytic cup for engulfment of the bead. This chemoattractant GPCR/Gi signaling works independently of phagocytic receptor/tyrosine kinase signaling to promote phagocytosis. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight against invading bacteria.

Sign in / Sign up

Export Citation Format

Share Document