Role of proline-rich tyrosine kinase 2 (Pyk2) in the pathogenesis of Alzheimer's disease

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common form of dementia in the elderly. Two major pathological hallmarks have been identified for AD: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFT). Recently, proline-rich tyrosine kinase 2 (Pyk2), which belongs to the focal adhesion kinase (FAK) non-receptor tyrosine kinase family, was recognized to contribute significantly towards the pathogenesis of AD. Pyk2 can influence the formation of amyloid plaques as well as NFTs. The kinase can directly phosphorylate tau, which is a significant component of NFTs and enhances tau pathology. Several competitive inhibitors have been developed for Pyk2, tested in several cancer models, as Pyk2 is known to be overexpressed under those conditions. The current review article discusses the possible mechanistic pathways by which Pyk2 can influence the pathogenesis of AD. Besides, it describes various inhibitors for Pyk2 and their potential role as therapeutics for AD in the future.