Calcium transporters and their role in the development of neuronal disease and neuronal damage.

Neurodegeneration comprises assembly of pathophysiological events that gives rise to a progressive loss of neuronal structure and function including cellular damage, diseases development or cellular death. Neurons respond by adjusting signaling pathways, from gene expression to morphological changes. In most of these processes, Ca2+ signaling plays a pivotal role. By increasing the Ca2+ concentration, the cell responds to neuronal, neurotrophic and other growth factor stimuli, however, the molecular mechanism of Ca2+-dependent neurite outgrowth and development yet requires further elucidation. Here we focus on the role of Ca2+ and selected Ca2+ transporters involved in processes of CNS neurodegeneration - inositol 1,4,5-trisphosphate (IP3Rs) and ryanodine receptors (RyRs), considering the fact that these receptors may be important "sensors" of disturbed intracellular calcium homeostasis. We propose that in vitro cellular models could serve as suitable experimental systems for the determination of the role that these receptors play in neuropathological conditions. Recognition of the principles, key players and regulatory processes may elucidate the role of Ca2+ in the regulation of neuronal proliferation, development and differentiation, growth and axon navigation in neurodegenerative and regenerative processes. This may provide a new insight and also discovery of novel therapeutic-targeting possibilities for severe neurological disorders and pathophysiological changes.