Glycogen synthase kinase‐3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder with diverse pathogenesis and notable cognitive impairments, characterized by Aβ aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, extensively analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function. It directly promotes tau phosphorylation, regulates amyloid precursor protein (APP) cleavage, leading to Aβ formation, and directly or indirectly triggers neuroinflammation and oxidative damage. We also summarize preclinical research highlighting the inhibition of GSK3 activity as a primary therapeutic approach for AD. Finally, pending issues like the lack of highly specific and affinity‐driven GSK3 inhibitors, are raised and expected to be addressed in future research. In conclusion, GSK3 represents a target in AD treatment, filled with hope, challenges, opportunities, and obstacles.

Stroke is the second most common cause of death globally and the leading cause of death in China. The pathogenesis of cerebral ischemia injury is complex, and oxidative stress plays an important role in the fundamental pathologic progression of cerebral damage in ischemic stroke. Previous studies have preliminarily confirmed that oxidative stress should be a potential therapeutic target and antioxidant as a treatment strategy for ischemic stroke. Emerging experimental studies have demonstrated that polyphenols exert the antioxidant potential to play the neuroprotection role after ischemic stroke. This comprehensive review summarizes antioxidant effects of some polyphenols, which have the most inhibition effects on reactive oxygen species generation and oxidative stress after ischemic stroke.

Hexokinase 2 (HK2) is widely distributed in various tissues, particularly showing significantly elevated expression levels in tumor tissues. As the initial rate-limiting enzyme in the glycolysis process, HK2 is believed to directly participate in the metabolic reprogramming of tumor cells. This phenomenon, known as the “Warburg effect,” provides the energy and substances necessary for the rapid proliferation, growth, and division of tumor cells. Furthermore, by enhancing glycolysis, HK2 exerts its influence on various metabolic pathways in tumor cells, such as pentose phosphate metabolism, glutamine metabolism, serine metabolism, and glycine metabolism, thereby playing a role in the occurrence and development of cancer. Therefore, HK2 represents a promising target for cancer therapy. Simultaneously, natural products with effects on inhibiting the expression or activity of HK2, have already been discovered to exhibit significant anticancer potential. Flavonoids, pentacyclic triterpenoids, phenolic compounds, and lignans constitute the majority of these natural products, directly inhibiting HK2 or indirectly downregulating it through protein kinase B (AKT), hypoxia-inducible factor 1 alpha (HIF-1α), and c-Myc signaling pathways. However, several challenges remain, such as further screening for natural products that directly target and inhibit HK2, optimizing the selection of natural product inhibitors for HK2, and elucidating the molecular mechanisms by which natural products indirectly inhibit HK2. In conclusion, the potential of targeting HK2 for cancer therapy is promising, and with these challenges addressed, natural products inhibiting HK2 will play an even greater role in the fight against cancer.