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Journal of Neuroscience, Vol 15, 7727-7733, Copyright © 1995 by Society for Neuroscience
Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
Y Sagot, M Dubois-Dauphin, SA Tan, F de Bilbao, P Aebischer, JC Martinou and AC Kato
Department of Pharmacology, Centre Medical Universitaire, Geneva, Switzerland.
Bcl-2 and its analogs protect different classes of neurons from apoptosis
in several experimental situations. These proteins may therefore provide a
means for treatment of neurodegenerative diseases. We examined the effects
of Bcl-2 overexpression in a genetic mouse model with motor neuron disease
(progressive motor neuronopathy/pmn). Pmn/pmn mice lose motoneurons and
myelinated axons, and die at 6 weeks of age. When these mice were crossed
with transgenic mice that overexpress human Bcl-2, there was a rescue of
the facial motoneurons with a concomitant restoration of their normal soma
size and expression of choline acetyltransferase. However, Bcl-2
overexpression did not prevent degeneration of myelinated axons in the
facial and phrenic motor nerves and it did not increase the life span of
the animals. Since Bcl-2 acts strictly on neuronal cell body survival
without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this
proto- oncogene would not in itself be sufficient for treatment of
neurodegenerative diseases where axonal impairment is a major component.
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