Recent medicinal chemistry efforts of targeting protein kinases for treating neurological conditions of Parkinson's and Alzheimer's diseases.

The human genome encodes a wide variety of protein kinases that regulate multiple cellular functions. These enzymes play a crucial role in amplifying and propagating intracellular signals during signal transduction. Dysregulation of protein kinase signaling is associated with vascular diseases, inflammatory disorders, cancer, and various neurological conditions. Kinase-targeted therapies have already demonstrated clinical efficacy in oncology and inflammatory diseases, prompting growing interest in their potential application in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Several kinases, including PDK1, CK1, CK2, c-Abl, p38 MAPK, PKA, GSK-3β, PINK1, and ROCK, have been implicated in the pathogenesis of AD and PD, highlighting their potential as therapeutic targets. However, the development of kinase inhibitors for central nervous system (CNS) disorders remains challenging due to limited blood-brain barrier (BBB) penetration and cytochrome P450-mediated metabolism. This review summarizes protein kinase targets involved in AD and PD, discusses kinase inhibitors under preclinical and clinical investigation, and highlights emerging strategies to overcome pharmacokinetic and therapeutic limitations in the development of disease-modifying therapies.