Detalle de: Chapter 9. Tau Protein Kinases Inhibitors: From the Bench to the Clinical Trials

Tau protein promotes microtubule assembly and stabilization what enables neurites extension and steadiness. Tau abnormally hyperphosphorylated is the major component of paired helical filaments (PHFs) which form a compact filamentous network called neurofibrillary tangles (NFTs). These NFTs have been described in different neurodegenerative diseases (known as tauopathies) such as Alzheimer's Disease (AD), Pick's disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis. Abnormal hyperphosphorylation of tau protein is regulated by protein kinases and phosphatases. Several protein kinases were identified as responsible for tau protein phosphorylation in vitro in approximately 15 different sites. These proteins were the glycogen synthase kinase 3β (GSK-3β) and the cyclin-dependent kinase 5 (CDK5). Other kinases involved in the phosphorylation process were casein kinase 1delta (CK-1δ), mitogen-activated protein kinases (MAPKs), cAMP-dependent protein kinase (PKA), and calcium/calmodulin-dependent protein kinase II (CaMKII). Due to the implications of tau phosphorylation in AD and other neurodegenerative diseases, the discovery of new kinase inhibitors have become an emerging target for these diseases entering some of them into clinical trials. In this section, different kinase inhibitors will be discussed.