A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice

• DOI: 10.1016/j.isci.2025.112200
• Publication Date: 2025-03-11T16:57:44Z
• Authors: Sangita Paul; Remya Chandran; Dileep K. Vijayan; Juhi Bhardwaj; Praveen Singh; Poornima Shetty; Srinivas Cheruku; Sajith Meleveetil; Binukumar Balacha...
• Keywords: Cyclin-dependent kinase 5

Type 2 diabetes (T2D) is a metabolic disorder commonly linked with cognitive decline, increasing patients' susceptibility to dementia. Alzheimer's disease (AD) has strong connection hyperglycemia and insulin dysregulation. Interestingly, certain anti-diabetic drugs have shown potential in reducing T2D-induced impairment. Previous studies, including ours, highlighted the dysregulation of cyclin-dependent kinase 5 (Cdk5) activity both T2D AD, which may contribute pathological changes these conditions. Thus, targeting Cdk5 could offer therapeutic approach for deterioration. Our research identifies as key link between decline. By screening KINACore library, we discovered two new brain-penetrant inhibitors, BLINK11 BLINK15. In high-fat diet-induced model, inhibitors improved blood glucose levels, obesity, function. BLINK11, particular, shows promise candidate treating impairment associated T2D.