A calcium sensor helps save damaged neurons, as reported by Nakamura et al. (page 1081).
Calcium is a favorite messenger of neurons—it regulates neurotransmission, signal transduction, and synapse plasticity. The calcium-binding protein NCS-1 translates increased intracellular calcium levels into many of these downstream outcomes. The new results show that NCS-1 also activates antiapoptotic pathways in neurons.
Neuronal apoptosis can result from injury or infection. Neurons often survive these insults, however, thanks to activation of the Akt survival pathway by neurotrophic factors such as GDNF. The authors show that this effect requires NCS-1, which is induced by GDNF. When activated by calcium (whose cytoplasmic levels probably increase upon injury), NCS-1 is known to activate phosphoinositide kinases that produce Akt substrates, thus jumpstarting the survival pathway.
Loss of NCS-1 hastened cell death in injured rat brains. It also hampered the long-term survival of neurons under normal culture conditions, suggesting that low levels are required even in the absence of injury. As injury strongly increases the levels of NCS-1, its overexpression did not improve survival further. But in diseases in which neuronal survival and regeneration is impaired, boosting NCS-1 activity might have benefical effects.