Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

摘要

Stroke is a debilitating disease that affects millions each year. White in many cases cerebral ischemic injury can be limited by effective resuscitation or thrombolytic treatment, the injured neurons wither in a process known as delayed neuronal death (DND). Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered. Of particular interest are two groups of signal proteins ihat participate in apoptosis-cyclin dependent kinases (CDKs) and p53-among a myriad of signaling events after an ischemic insult. Recent investigations have shown that CDKs, a family of enzymes initially known for their role in cell cycle regulation, are activated in injured neurons in DND. As for p53, new reports suggest that its up-regulation may represent a failed attempt to rescue injured neurons, although its up-regulation was previously considered an indication of apoptosis.These observations tints rekindle an old quest to identify new neuroprotective targets to mini-mize the stroke damage. In this review, the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target. Finally, using CDK inhibition as an example, this paper will discuss the pertinent criteria for a viable neuroprotective strategy for iscliemic injury.