Signaling pathways and promising small-molecule therapeutic agents for Ischemic Stroke.

Abstract

Stroke is the second highest cause of death and leading cause of disability with the high economic burden worldwide. The incidence of stroke is increasing faster and more prevalent for the global population over age 65. Ischemic stroke (IS) has a higher incidence than hemorrhagic stroke, accounting over 80% of the total incidence of stroke. The incidence rate of ischemic stroke is increasing in all age groups and both sexes. In the modern era, hypertension, high blood pressure and lifestyle are considered as the causes of the disease. Compared to severity, the treatment options for stroke is still limited, mainly thromolytic and thrombectomy therapy. In the past decade, a number of therapeutic agents have been studied for neuroprotection in the acute ischemic stroke to protect the brain from ischemic injury. Several study methods focus to improve neurons functions around the ischemic core and protect from the shock. Many signaling pathways including NF-kB, NrF, Nrf2-Keap1, PI3K/AKT, JAK/STAT signaling pathways are strongly associated for the indication. Controlling the signaling pathways by small molecules potentially improve the neuronal functions. In this article, we review the recent advancement of the drug discovery, controlling signaling pathways by small molecules, and kinase inhibitors in this direction.