Fig. 3.

The accumulated damage model of neurodegeneration due to defective DNA repair. For explanation see text. For the neurodegenerative diseases in Table 1, the time necessary for accumulated DNA damage to reach the neuronal death threshold is likely to be several years, if not longer. This may explain why the Atm^−/−, Xpa^−/− and Aptx^−/− mice do not accurately reproduce the progressive neurodegeneration observed in the human patients; the 2-year lifespan of a mouse is simply not long enough to allow sufficient damage to accumulate (see also [10]).