Abstract
Alzheimer’s disease (AD) is a type of progressive neurodegenerative disease, and amyloid β-protein 42 (Aβ42) serves an important role in the pathological process of development of AD. Paired immunoglobulin-like receptor B (PirB) is a functional receptor for myelin inhibitors of neuron regeneration in the CNS, and it has also been identified to function as a high-affinity receptor for Aβ. Here, we used a phage display to identify a specific PirB antagonist peptide 11(PAP11, PFRLQLS), which could reverse Aβ42-induced neurotoxicity and promote neurite outgrowth in vitro. Immunofluorescence analysis showed that PAP11 colocalized with PirB on the membrane of cortical neurons. Horseradish peroxidase-streptavidin-biotin assay further proved that PAP11 directly binds to PirB and the dissociation constant (Kd) was 0.128μM. PAP11 functionally antagonized the neurite outgrowth inhibitory effect induced by Aβ42 in cortical neurons, and the underlying mechanism was associated with a PirB-ROCK2/CRMP2 signaling pathway. The novel PirB antagonist peptide PAP11 may be a promising candidate therapeutic agent for the treatment of AD and other neurodegenerative diseases.
Key points
• PAP11 was the first PirB antagonist peptide screened by phage display technology.
• PAP11 could protect neurons by blocking the binding of Aβ42 and PirB.
• PAP11 reverse inhibitory effect of neurite outgrowth through ROCK2/CRMP2 pathway.
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Data availability
The data generated during and/or analyzed during the current study are available from the corresponding author on reasonable request
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Funding
The study was funded by the National Natural Science Foundation of China (grant nos. 81202519, 81903617), the Science and Technology Program of Guangzhou (grant no. 202002030079), the Natural Science Foundation of Guangdong Province (grant no. 2019A1515010936), and the Fundamental Research Funds for the Central Universities (grant no. 11620425 to JZ).
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F. X., J. L., and Zd. Z. designed the experiments. Z. Z., Z. W., and Z. L. performed all the experiments. Z. Z., Z. W., Y. L., Q. G., and L. Y. analyzed the data. Z. Z. and Z. W. wrote the manuscript. J. Z., Zd. Z., and J.L. revised the manuscript. All authors have read and approved the final manuscript.
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Zhang, Z., Wang, Z., Ling, Z. et al. A screened PirB antagonist peptide antagonizes Aβ42-mediated inhibition of neurite outgrowth in vitro. Appl Microbiol Biotechnol 105, 4649–4662 (2021). https://doi.org/10.1007/s00253-021-11363-2
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DOI: https://doi.org/10.1007/s00253-021-11363-2