A Chemical Knock Down of p38 MAPK as a Novel Therapeutic Approach to Alzheimer’s Disease

  P38 MAPK (Mitogen-Activated Protein Kinase) has been considered as a crucial target for chronic inflammatory diseases such as rheumatoid arthritis for past decades. However, targeting the kinase has not been relevant with its clinical utility for the diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid-beta plaques and tau-aggregated neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the modulation of p38 MAPK is a promising strategy for the treatment of AD. Recently, we developed a novel approach to AD by degrading p38 MAPK. In particular, p-p38 MAPK, p38 MAPK active form causing downstream activation as well as aggravating its pathology in the chronic inflammation, is selectively degraded by our approach. In addition, we confirmed that this novel approach is effective for the treatment of AD in the 5X-FAD mouse model. In this seminar, overall strategy towards AD using the selective chemical degradation of p-p38 MAPK will be presented.

20210318_대학원세미나_김남중 교수.pdf