Unknown

Dataset Information

0

Poly-arginine and arginine-rich peptides are neuroprotective in stroke models.


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.

SUBMITTER: Meloni BP 

PROVIDER: S-EPMC4640246 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC7052017 | biostudies-literature
| S-EPMC5905407 | biostudies-literature
| S-EPMC9259545 | biostudies-literature
| S-EPMC8421406 | biostudies-literature
| S-EPMC3466390 | biostudies-literature
| S-EPMC6094173 | biostudies-literature
| S-EPMC2635027 | biostudies-literature
| S-EPMC8581540 | biostudies-literature
| S-EPMC8618101 | biostudies-literature
| S-EPMC7147261 | biostudies-literature