The darker side of Ca2+ signaling by neuronal Ca2+-sensor proteins: from Alzheimer's disease to cancer

Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these proteins also have key roles in pathological processes of disease. Thus, a 'darker side' of NCS protein signaling has become evident in some CNS disorders, such as Alzheimer's disease and schizophrenia, and in cancer. In this article, I will provide an overview of the current, and rapidly expanding, knowledge of how this important family of proteins might be involved in various major CNS diseases, the proposed role of NCS proteins in pathophysiological signaling and the development of pharmacological tools and novel research strategies.