Rny12 peptidomimetic increases sh-sy5y neuronal survival comparable to bdnf

Fatemeh Nafian,1,* Mohammad javad,2 Shahin yazdani,3 Zahra soheila soheili,4

1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University
2. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University
3. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences
4. Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology



Brain-derived neurotrophic factor (bdnf) activates downstream cell signaling pathways through trkb receptor and triggers key functions to neuronal survival. nowadays, bdnf have been suggested as a potent therapeutic candidate for neurodegenerative diseases. however, there are several clinical concerns about its therapeutic applications.


In the current study, we designed and developed bdnf-mimicking small peptide (named as rny12) using phage-display technology, as an alternative to circumvent these problems. the affinity binding this peptidomimetic was assessed by testing against the native structure of trkb in sh-sy5y cells in vitro using flow-cytometry, respectively. we also used atra-treated sh-sy5y cells in serum-free medium which neuronal survival was dependent on continuous presence of bdnf. we treated them with rny12, while bdnf served as a positive control.


When sh-sy5y cells were treated by atra and bdnf, they revealed a trkb overexpression (5 ± 0.08165, n=3) compared to untreated cells (1 ± 0.04223, n=3) using real-time pcr. similarly, an increase fluorescence intensity was detected due to fitc-conjugated rny12 binding to the trkb receptors on treated (14.28 ± 0.01667, n=3) versus untreated (4.443 ± 0.04978, n=3) cells using flow-cytometry. based on mtt assays, our peptidomimetic demonstrated equal or even greater neuroprotective efficacy as compared to bdnf.


Under these conditions, rny12 may activate one or more trkb dependent signaling pathways to resume cell cycle. this implies that rny12 can mimic bdnf activities in vitro due to its unique sequence. small size of rny12 might be an advantage for drug design and synthesis in future.


Bdnf; neurodegenerative diseases; neuronal survival; trkb agonist; phage-displayed peptide library