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

Abstract

Abstract. 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, Ca 2+ signaling plays a pivotal role. By increasing the Ca 2+ concentration, the cell responds to neuronal, neurotrophic and other growth factor stimuli, however, the molecular mechanism of Ca 2+ -dependent neurite outgrowth and development yet requires further elucidation.Here we focus on the role of Ca 2+ and selected Ca 2+ transporters involved in processes of CNS neurodegeneration -inositol 1,4,5-trisphosphate (IP 3 Rs) 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 Ca 2+ 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.

Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function

“…We have previously shown that in non-excitable cells, TRPM7 is tightly regulated with cellular Mg 2+ concentration [19]; however, its role in n e u r o t o x i n m o d e l s o f P D i s n o t w e l l s t u d i e d . Neurodegeneration comprises the assembly of several pathological events that could lead to a progressive loss of neuronal structure and function including cellular damage, disease development, or cellular death [20]. Importantly, most of these processes are dependent on Mg 2+ and as TRPM7 regulates Mg 2+ homeostasis, it could be postulated that TRPM7 would play a major role in these conditions.…”

The methyl-CpG-binding domain (MBD) is crucial for MeCP2’s dysfunction-induced defects in adult newborn neurons

“…Spontaneous Ca 2+ oscillations occur as a result of periodical increase and decrease of the free Ca 2+ (Garaschuk et al, 2000 ; Berridge et al, 2003 ; Okubo et al, 2011 ), and have been shown to occur in many different neuronal types and at different stages of maturation (Owens et al, 2000 ; Marchetto et al, 2010 ; Linde et al, 2011 ) and are thought to play critical roles in neuronal development and plasticity (Clapham, 1995 ; Jaskova et al, 2012 ). A previous study also showed that spontaneous Ca 2+ oscillations encode information in their frequency to regulate neurotransmitter expression, channel maturation and neurite extension in spinal neurons (Gu and Spitzer, 1995 ).…”

TRPM7 and its role in neurodegenerative diseases

“…Neurodegeneration comprises the assembly of pathological events that give rise to a progressive loss of neuronal structure and function including cellular damage, diseases development, or cellular death. 64 In most of these processes, Ca 2+ and Mg 2+ play a pivotal role and as TRPM7 regulates both these ions it can be postulated that TRPM7 will play a major role in these conditions ( Fig. 1 ).…”