Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries

Abstract

Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein–protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood–brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke.

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

“…These agents include anti-inflammatory factors, antioxidants, glutamate antagonists, neurotrophic factors, γ-aminobutyric acid receptor agonists, calcium antagonists, and free radical scavengers. 27 , 28 These neuroprotective medicines have shown promise in improving the prognosis of ischemic stroke in several preclinical and clinical trials; nevertheless, these results must be further validated and standardized. This necessity arises due to various factors, such as the heterogeneity of stroke in human subjects, the evaluation metrics employed in animal studies, the optimal time window for drug administration, and the influence of brain aging on treatment outcomes.…”

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

“…Neuroprotective peptides have the ability to diminish brain damage and facilitate healing after a stroke [ 180 , 181 ]. Nevertheless, transporting them to the brain is difficult because of the BBB.…”

Membrane-Active Peptides and Their Potential Biomedical Application

“…TAT and other neuroprotective peptides coupled to CPPs are effective in various acute neurodegenerative diseases such as traumatic brain injury, stroke, and prenatal hypoxia–ischemia [ 139 ]. One of the primary mechanisms triggering neuronal degeneration in stroke is known to be excessive glutamate release from synaptic junctions and related cytotoxicity [ 140 , 141 ]. Studies show that the polyarginine ST2-104 peptide may prevent glutamate-induced cell death in SH-SY5Y neuroblastoma cells, modulate calcium intake, and avoid apoptosis and autophagy.…”

“…Studies show that the polyarginine ST2-104 peptide may prevent glutamate-induced cell death in SH-SY5Y neuroblastoma cells, modulate calcium intake, and avoid apoptosis and autophagy. It is also known that the arginine-rich R18 peptides (polyarginine-18, L-isomer, and D-isomer) boost the optimum activity of the thrombolysis response while preserving their neuroprotective qualities when co-administered with thrombolytic drugs [ 140 ]. While it is undoubtedly true that the arginine content of the peptide is significant in this regard, it is also notable that other amino acid residues can affect peptide behavior.…”