Question

In the central nervous system (CNS), traumatic injury can trigger apoptosis. Draw and/or describe the molecular pathway; and then describe a real or hypothetical drug treatment that would prevent this pathway activation. What would be the target of your drug and how would it affect this pathway?

Answer 1

When there is a damage or injury occurred to central nervous system, apoptotic cells will get activated and it will start degenerate the cells. After some weeks of brain injury, neutrons undergoes apoptosis during post acute traumatic period. Apoptotic oligodendrocytes and astrocytes will be observed in the brain area.

In traumatic brain injury, apoptosis is induced by Caspase 3 activation. Almost after 4 hours of injury, DNA fragmentation will be observed. At this time, a 4 to 5 fold increase in Caspase 3 mRNA levels will be observed and 25 to 50 percent increase in Caspase 3 enzyme activity. Hence the target for reduction of apoptosis is Caspase 3 activity. Therefore application of DEVD-fmk after the injury will reduce the apoptosis, hence reduce cell loss and lesion volume.

In spinal cord injury, apoptosis is induced by both Caspase 3 and 9 activity in the cells of spinal cord. This apoptosis pathway will be prevented by administering intrathecal injection of Caspase 3 inhibitor like z-DEVD-fmk an hour before the injury.