Cell Cycle Regulation in Neurodegenerative Diseases
The focus of my lab is on the regulation of cell cycle events in mature ‘postmitotic’ neurons. Our work has lead to the perspective that neurons must constantly suppress the cell cycle once they complete neurogenesis. If they fail to do so they will re-enter a cycle they will not be able to complete. These ‘cycling’ neurons are consigned to one of two fates depending on their stage of maturation. The first is found in young differentiating neurons. In these cells re-entrance into a cycle leads to death within hours, and inhibition of the cell cycle blocks this death. In adult neurons, however a second fate is observed. Re-entrance into a cycle leads to expression of cell cycle proteins and DNA replication, but for many months the neurons appear incapable of either completing the cycle or dying. This work has clinical relevance as the linkage between cell cycle and cell death appears to lie at the root of many human neurodegenerative diseases. Two that we have investigated include Alzheimer’s disease and Ataxia-Telangiectasia. We are currently exploring the multi-tiered strategy the neurons use to suppress the cell cycle: genomic rearrangements are strongly suggested, cell cycle proteins are found in unexpected locations, proteins switch function from cell cycle promoters to cell cycle suppressors.