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Review
. 2021 Sep 10;403(1):27-41.
doi: 10.1515/hsz-2021-0258. Print 2022 Jan 26.

Emerging contributions of formyl peptide receptors to neurodegenerative diseases

Lukas Busch  1 , Stefan Vieten  1 , Susan Brödel  1 , Kristina Endres  2 , Bernd Bufe  1
Affiliations
Free article
Review

Emerging contributions of formyl peptide receptors to neurodegenerative diseases

Lukas Busch et al. Biol Chem. .
Free article

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.

Keywords: Alzheimer’s disease; FPR; biased agonism; neuroinflammation.

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References

    1. Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., MacVicar, B.A., and Newman, E.A. (2010). Glial and neuronal control of brain blood flow. Nature 468: 232–243, https://doi.org/10.1038/nature09613.
    1. Bailey-Bucktrout, S.L., Caulkins, S.C., Goings, G., Fischer, J.A.A., Dzionek, A., and Miller, S.D. (2008). Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J. Immunol. 180: 6457–6461, https://doi.org/10.4049/jimmunol.180.10.6457.
    1. Becker, E.L., Forouhar, F.A., Grunnet, M.L., Boulay, F., Tardif, M., Bormann, B.J., Sodja, D., Ye, R.D., Woska, J.R., and Murphy, P.M. (1998). Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells. Cell Tissue Res. 292: 129–135, https://doi.org/10.1007/s004410051042.
    1. Beers, D.R., Henkel, J.S., Xiao, Q., Zhao, W., Wang, J., Yen, A.A., Siklos, L., McKercher, S.R., and Appel, S.H. (2006). Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U.S.A. 103: 16021–16026, https://doi.org/10.1073/pnas.0607423103.
    1. Bihler, K., Kress, E., Esser, S., Nyamoya, S., Tauber, S.C., Clarner, T., Stope, M.B., Pufe, T., and Brandenburg, L.O. (2017). Formyl peptide receptor 1-mediated glial cell activation in a mouse model of cuprizone-induced demyelination. J. Mol. Neurosci. 62: 232–243, https://doi.org/10.1007/s12031-017-0924-y.

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