Adenosine Kinase is a New Therapeutic Target to Prevent Ischemic Neuronal Death

摘要

The brain has evolved several endogenous mechanisms to protect itself from the deleterious consequences ofstroke. One of these endogenous neuroprotective systems is centered on the purine ribonucleoside adenosine, which exertspotent neuroprotective functions within the brain. One major goal in stroke research is to explore and utilize suchendogenous neuroprotective mechanisms therapeutically. This review illustrates molecular approaches to study the role ofthe adenosine system within the context of stroke and highlights innovative therapeutic approaches aimed at increasingadenosinergic function. New research data suggest that the major adenosine regulating enzyme adenosine kinase (ADK)plays a prominent role in determining the brain’s susceptibility to ischemic injury. Endogenous ADK is rapidlydownregulated following a stroke, possibly an endogenous neuroprotective mechanism aimed at raising ambient levels ofadenosine in the brain. Conversely, transgenic overexpression of ADK in the brain renders the brain more susceptible tostroke-induced neuronal cell loss. In the present review we will first summarize the physiological role of adenosinemetabolism within the context of ischemic brain injury. Next, we will highlight the key role of ADK in determining thebrain’s susceptibility to ischemic injury, and finally we will discuss potential therapeutic applications of adenosineaugmentation to provide neuroprotection in stroke.