BCL-2 OVEREXPRESSION PREVENTS MOTONEURON CELL BODY LOSS BUT NOT AXONAL DEGENERATION IN A MOUSE MODEL OF A NEURODEGENERATIVE DISEASE

Bcl-2 and its analogs protect different classes of neurons from apopto sis in several experimental situations, These proteins may therefore p rovide a means for treatment of neurodegenerative diseases, We examine d the effects of Bcl-2 overexpression in a genetic mouse model with mo tor 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 B cl-2, there was a rescue of the facial motoneurons with a concomitant restoration of their normal soma size and expression of choline acetyl transferase, However, Bcl-2 overexpression did not prevent degeneratio n of myelinated axons in the facial and phrenic motor nerves and it di d not increase the life span of the animals, Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degener ation in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself b e sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.