Notch and presenilins in vertebrates and invertebrates: implications for neuronal development and degeneration

Recent progress in elucidating the biology of Notch and presenilin has revealed a close functional relationship between these two proteins during cell fate determination in worms, flies and humans. Presenilins are required for the putatively intramembranous proteolysis of Notch to release its intracellular domain to the nucleus. This finding establishes a specific biochemical role for presenilins in Notch signaling and interfaces with emerging evidence about how frizzled, disheveled and numerous other genes regulate the highly complex Notch pathway. Advances in understanding Notch and presenilin functions in the differentiation of neurons and non-neural cells have important implications not only for development but also for late-life degenerative disorders such as Alzheimer's disease.