This review explains that a group of receptors called formyl peptide receptors (FPRs) play a big role in brain inflammation linked to diseases like Alzheimer’s. One of the natural proteins that can bind these receptors is humanin, which appears to protect brain cells. Blocking FPRs in experiments reduced inflammation, hinting that targeting this system could be a future way to support brain health.

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.