Computational modeling of kinases in the DLK-JNK signaling pathway: from conformational dynamics to inhibition mechanism

Abstract

Neurological diseases can be defined as a diverse group of disorders that affect the central and peripheral nervous systems, including conditions such as epilepsy, multiple sclerosis, stroke, neuropathies, and neurodegenerative diseases. These conditions account for a considerable proportion of global mortality, impacting millions of individuals worldwide. Neurological diseases are becoming more common due to an aging population, environmental exposures, and lifestyle modifications, typically resulting in chronic disability, cognitive decline, and reduced life quality1. Treatments available today for a variety of neurological disorders predominantly provide symptomatic relief, with limited capacity to influence disease progression. Furthermore, the presence of drug-related side effects and therapeutic resistance adds complexity to prolonged treatment management. Hence, the development of advanced and focused therapies is crucial for effectively addressing neurological diseases and improving clinical outcomes.