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Selected Works of Ryan Anderton
Article
Poly-arginine and arginine-rich peptides are neuroprotective in stroke models
Journal of Cerebral Blood Flow and Metabolism (2015)
  • Bruno Meloni, The University of Western Australia
  • Laura Brookes, The University of Western Australia
  • Vince W Clark, The University of Western Australia
  • Jane Cross, The University of Western Australia
  • Adam Edwards, Western Australian Neuroscience Research Institute
  • Dr Ryan Anderton, The University of Notre Dame Australia
  • Richard M Hopkins, The University of Western Australia
  • Katrin Hoffmann, The University of Western Australia
  • Neville Knuckey, Sir Charles Gairdner Hospital
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Abstract
Using cortical neuronal cultures and glutamic acid excitotoxicity and oxygen-glucose deprivation (OGD) stroke models, we
demonstrated that poly-arginine and arginine-rich cell-penetrating peptides (CPPs), are highly neuroprotective, with efficacy
increasing with increasing arginine content, have the capacity to reduce glutamic acid-induced neuronal calcium influx and require
heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect. Furthermore, neuroprotection could be
induced with immediate peptide treatment or treatment up to 2 to 4 hours before glutamic acid excitotoxicity or OGD, and with
poly-arginine-9 (R9) when administered intravenously after stroke onset in a rat model. In contrast, the JNKI-1 peptide when fused
to the (non-arginine) kFGF CPP, which does not rely on endocytosis for uptake, was not neuroprotective in the glutamic acid model;
the kFGF peptide was also ineffective. Similarly, positively charged poly-lysine-10 (K10) and R9 fused to the negatively charged
poly-glutamic acid-9 (E9) peptide (R9/E9) displayed minimal neuroprotection after excitotoxicity. These results indicate that peptide
positive charge and arginine residues are critical for neuroprotection, and have led us to hypothesize that peptide-induced
endocytic internalization of ion channels is a potential mechanism of action. The findings also question the mode of action of
different neuroprotective peptides fused to arginine-rich CPPs.
Disciplines
Publication Date
2015
DOI
10.1038/jcbfm.2015.11
Citation Information
Meloni, B., Brookes, L., Clark, V., Cross, J., Edwards, A., Anderton, R.S., Hopkins, R., Hoffmann, K., Knuckey, N. (2015). Poly-arginine and arginine-rich peptides are neuroprotective in stroke models. Journal of Cerebral Blood Flow and Metabolism, 35(6), 993-1004. DOI: 10.1038/jcbfm.2015.11