Nature 406, 195–199 (2000).
It has been questioned whether our neurodegeneration model was anticipated by Calne and co-workers1,2,3,4. Both groups related exponential neuronal loss to pathogenesis, but the models are radically different. We recognized that in neurodegeneration, exponential death kinetics mean that the risk of cell death remains constant with age. To accommodate constant risk, we proposed a one-hit model: the hit is a consequence of a neuron being in a high-risk (for example, mutant) state; a hit is a biochemical reaction within each single neuron, committing it to death at a random time. We noted that constant risk excludes cumulative intracellular damage as a disease mechanism.
Calne et al. proposed that in idiopathic Parkinsonism “An event [for example, infection] acts on the neuronal population over a brief period …[to initiate disease]”2. They excluded ongoing processes as causing idiopathic Parkinsonism2,4, but the role of cumulative intracellular damage was not addressed. Their focus on whole neuron populations and on events that act on them is notable, and complementary to but different from our model.
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Schulzer, M., Lee, C. S., Mak, E. K., Vingerhoets, F. J. G. & Calne, D. B. A mathematical model of pathogenesis in idiopathic parkinsonism. Brain 117, 509– 516 (1994).
Calne, D. B. Is idiopathic parkinsonism the consequence of an event or a process? Neurology 44, 5–10 ( 1994).
Lee, C. S. et al. Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis. Neurology 45, 435–439 (1995).
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Clarke, G., Collins, R., Leavitt, B. et al. addendum: A one-hit model of cell death in inherited neuronal degenerations. Nature 409, 542 (2001). https://doi.org/10.1038/35054107
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DOI: https://doi.org/10.1038/35054107
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