Dysregulation of genes that control cell-cycle progression and DNA repair is a 
hallmark of tumorigenesis. It is becoming increasingly apparent, however, that 
these defects also contribute to degeneration of post-mitotic neurons under 
certain conditions. The gene for ataxia-telangiectasia mutated (ATM) is a 
prototype for this dual mechanism of action, with loss-of-function mutations 
causing not only selective degeneration of cerebellar neurons but also increased 
susceptibility to breast cancer and hematologic malignancy. Increased dosage of 
amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia 
of Alzheimer type and may also contribute to acute leukemia and transient 
myeloproliferative disorder. The gene parkin, loss-of-function mutations in 
which account for about half of cases of early-onset Parkinson disease, has been 
identified as a candidate tumor suppressor gene by several groups. Parkin is 
deleted or downregulated in several tumor types, and its re-expression 
sensitizes derivative cell lines to inhibitors of cell-cycle progression. The 
overlap of molecular pathways implicated in cancer and neurodegeneration 
challenges long-held notions about differentiated cellular states and may open 
the door to novel therapeutic approaches to both groups of disorders.