METHODS OF USING HUMAN PROTEIN KINASE C DELTA VIII AS A BIOMARKER

摘要

RA treatment can improve cognition; promote neurogenesis; and regulate alternative splicing of genes, particularly by mediating mechanisms of 5' splice site selection and generation of PKCd alternatively spliced variants. Expression of PKCdVIII is an indicator of the levels of on-going apoptosis in neurons. In the aging brain, switching the isoform expression to PKCdVIII by RA could shield the cells from neuronal death. The inventors discovered that human PKCdVIII expression is increased in neuronal cancer and decreased in Alzheimer's disease. The data shows that PKCdVIII promotes neuronal survival and increases neurogenesis via Bcl2 and Bcl-xL. In addition, the trans-factor SC35 was found to be crucial in mediating the effects of RA on alternative splicing of PKCdVIII mRNA in neurons. The data described herein indicate that PKCdVIII can be used as a biomarker for neurological diseases such as cancers and Alzheimer's disease and as a tool for monitoring and evaluating treatment.