Apolipoprotein E-Mimetic Peptide COG1410 Promotes Autophagy by Phosphorylating GSK-3β in Early Brain Injury Following Experimental Subarachnoid Hemorrhage

Abstract

COG1410, a mimetic peptide derived from the apolipoprotein E (apoE) receptor binding region, exerts positive effect on neurological deficits in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). Currently the neuroprotective effect of COG1410 includes inhibiting BBB disruption, reducing neuronal apoptosis, and neuroinflammation. However, the effect and mechanism of COG1410 to subcellular organelles disorder have not been fully investigated. As the main pathway for recycling long-lived proteins and damaged organelles, neuronal autophagy is activated in SAH and exhibits neuroprotective effects by reducing the insults of EBI. Pharmacologically elevated autophagy usually contributes to alleviated brain injury, while few of the agents achieved clinical transformation. In this study, we explored the activation of autophagy during EBI by measuring the Beclin-1 and LC3B-II protein levels. Administration of COG1410 notably elevated the autophagic markers expression in neurons, simultaneously reversed the neurological deficits. Furthermore, the up-regulated autophagy by COG1410 was further promoted by p-GSK-3β agonist, whereas decreased by p-GSK-3β inhibitor. Taken together, these data suggest that the COG1410 might be a promising therapeutic strategy for EBI via promoting autophagy in SAH.

Apolipoprotein E-Mimetic Peptide COG1410 Enhances Retinal Ganglion Cell Survival by Attenuating Inflammation and Apoptosis Following TONI

“…The therapeutic window for the treatment of acute brain injury animals expands to 2 h (Laskowitz et al, 2007), making it a potential protective agent for optic nerve injury treatment via intravenous administration. Several studies, including our previous research, assessed the neuroprotective effects of COG1410 on acute brain injury (Jiang and Brody, 2012; Li X. et al, 2018; Pang et al, 2018). COG1410 decreases JNK phosphorylation, iNOS protein levels and Bax expression, suggesting that COG1410 suppresses apoptosis possibly via inhibiting the p-JNK relative pathway.…”

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

“…For example, experiments have shown that both apoptosis and autophagy are activated in response to metabolic stress (Shliapina et al., 2021) or exposure to reactive oxygen species (Poillet‐Perez et al., 2015). Besides, autophagy pathway in brain is activated after the experimental subarachnoid hemorhage (SAH), which plays an important role in its EBI (Li X. et al., 2018). Autophagy precedes apoptosis, which has a protective effect in the early stages of programmed cell death (Jellinger & Stadelmann, 2000).…”

“…Besides, autophagy pathway in brain is activated after the experimental subarachnoid hemorhage (SAH), which plays an important role in its EBI (Li X. et al, 2018). Autophagy precedes apoptosis, which has a protective effect in the early stages of programmed cell death (Jellinger & Stadelmann, 2000).…”

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

“…Vitek et al examined the effects of this APOE mimetic in a mouse model of AD, and found that the peptide ameliorates behavioral deficits and reduces plaques and tangles [193]. COG1410 was recently shown to upregulate autophagy via phosphorylation of GSK3β [194]. Given the fact that GSK3β regulates tau phosphorylation, this finding may present one of the mechanisms underlying the effects of COG1410 on the tangle pathology.…”