ATP Running Amok

I know I promised something yesterday, but a 42.9 mi (69.0 km) bike ride averaging 19.7 mi/hr (31.7 km/hr) and climbing over 2700 ft (823 m) really drained me for the day. I did another 30 mi today at a killer pace thanks to the same group really pushing my current limits, but I feel great and ready to start another week. Here is a post as promised.

Although this story was released last week, it is the Nature Medicine August cover story: Scientists Finger Surprise Culprit In Spinal Cord Injury. Well, what wrecks havoc at the site of a spinal cord injury, often resulting in debilitating, permanent paralysis? ATP, a versatile molecule that powers events ranging from protein folding and processing to intra- and inter-cellular signaling. Clearly, ATP’s high-energy phosphate groups also serve a negative function, turning this life-giving molecule into a killing machine:

The finding that ATP is a culprit in causing the devastating damage of spinal cord injury is unexpected. Doctors have known that initial trauma to the spinal cord is exacerbated by a cascade of molecular events over the first few hours that permanently worsen the paralysis for patients. But the finding that high levels of ATP kill healthy cells in nearby regions of the spinal cord that were otherwise uninjured is surprising and marks one of the first times that high levels of ATP have been identified as a cause of injury in the body.

Using mouse models, the study shows that by inhibiting the effects of ATP neurons, mice who suffered spinal cord injuries recovered much of their original function. This provides great hope that people who suffer such injuries may one day be treated within minutes, preventing the hazardous effects of ATP.

I do not have access to the original article, but the press release touches briefly on the origin of ATP in the spinal cord. Interestingly, astrocytes, a type of support neuron, produce ATP in high quantities. In addition, neurons in the spinal cord have a so-called “death receptor” to which can ATP bind that activates a internal signaling pathway triggering death. The rupture of these astrocytes may well release the ATP, leaving it to cause the death of neurons and further harm the accident victim. This sort of activity is very similar to activity found on the cellular level around a cut or scratch. When cells around a wound rupture, they release their contents including various enzymes and ATP, damaging other nearby cells and causing a cascade of events resulting in a clot and arrival of immune cells to ward off infection.

This analogous activity in the spinal cord is somewhat puzzling from an evolutionary standpoint. Clearly, scientists have not yet learned of any function ATP serves in healthy individuals vis-à-vis these death receptors (or this study would not have been as surprising), so now attention must turn to understanding what “normal” purpose this receptor serves during the lifetime of a neuron. I might hypothesize that this may exist simply for programmed cell death upon reaching a certain age. Then again, I might be proven wrong and the real result may be just as unexpected as this discovery here today.