Journal Article

Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model

Knuckey, Neville W., Anderton, Ryan S., Edwards, Adam B., Meloni, Bruno P.

2017

Overview

In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with d -amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1–6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Amino acids / Analysis / Animals / Apoptosis / Arginine / Biochemistry / Biomedical and Life Sciences / Calcium Signaling - drug effects / Cardiology / Cellular biology / Cerebral Cortex - metabolism / Cerebral Cortex - pathology / Glutamate / Glutamic Acid - toxicity / Life Sciences / Medical Biochemistry / Neurobiology / Neurons / Neurons - metabolism / Neurons - pathology / Neuroprotective Agents - chemistry / Neuroprotective Agents - pharmacology / Oncology / Peptides / Peptides - chemistry / Peptides - pharmacology / Rats / Studies / Toxicity