Research Projects

Glycogen synthase kinase (GsK3beta) is a multifunctional serine or threonine kinase that regulates glycogen metabolism and functions in cell division, stem cell renewal, apoptosis, differentiation, transcription, and insulin action. It is a key target for developing new anti-Alzheimer agents due to its role in tau oligomerization and neuroinflammation. Alzheimer's disease (AD) is a multifactorial disease, with neurofibrillary tangles due to hyperphosphorylated tau and neuroinflammation being major pathological hallmarks. GsK3beta promotes microglial migration and inflammatory activation, and inhibiting it can increase anti-inflammatory cytokines and decrease pro-inflammatory cytokines. Recently, a structure-guided drug design approach was used to develop molecular hybrids of pyrazine and substituted diphenylmethylpiperazine as multi-target-directed ligands for AD treatment. The proposed study aims to optimize the identified lead molecule 21 for potential GsK3beta inhibitors targeting neuroinflammation and tau oligomerization, potentially targeting multiple disease-causing factors.