Delaying caspase activation by Bcl-2: A clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis.

摘要: Molecular mechanisms of apoptosis may participate in motor neuron degeneration produced by mutant copper/zinc superoxide dismutase (mSOD1), the only proven cause amyotrophic lateral sclerosis (ALS). Consistent with this, herein we show that spinal cord transgenic mSOD1 mice is site sequential activation caspase-1 and caspase-3. Activated caspase-3 its beta-actin cleavage fragments are found apoptotic neurons anterior horn affected mice; although such few, their scarcity should not undermine potential importance overall mSOD1-related neurodegeneration. Overexpression anti-apoptotic protein Bcl-2 attenuates neurodegeneration delays caspases fragmentation beta-actin. These data demonstrate caspase occurs this mouse model ALS during Our study also suggests modulation activity provide protective benefit treatment ALS, a view consistent our recent demonstration inhibition extending survival mice.