RT Journal Article
SR Electronic
T1 Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7727
OP 7733
DO 10.1523/JNEUROSCI.15-11-07727.1995
VO 15
IS 11
A1 Sagot, Y
A1 Dubois-Dauphin, M
A1 Tan, SA
A1 de Bilbao, F
A1 Aebischer, P
A1 Martinou, JC
A1 Kato, AC
YR 1995
UL http://www.jneurosci.org/content/15/11/7727.abstract
AB 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.