Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

王伏虎

摘要：Stroke is a debilitating disease that affects millions each year. While in many cases cerebral ischemic injury can be limited by effective resuscitation or throrrdoolytic treatment, the injured neurons wirher 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 istriggered. Of particular interest are two qroups of signal proteins that participate in apoptosis-cyelin 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 rescne injured neurons, although its up-regulation was previously considered an indication of apoptosis. These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage. In this review, the authzor 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 ischemic injury.