Calcium Dysregulation and Homeostasis of Neural Calcium in the Molecular Mechanisms of Neurodegenerative Diseases Provide Multiple Targets for Neuroprotection

Abstract

The intracellular free calcium concentration subserves complex signaling roles in brain. Calcium cations (Ca 2+ ) regulate neuronal plasticity underlying learning and memory and neuronal survival. Homo-and heterocellular control of Ca 2+ homeostasis supports brain physiology maintaining neural integrity. Ca 2+ fluxes across the plasma membrane and between intracellular organelles and compartments integrate diverse cellular functions. A vast array of checkpoints controls Ca 2+ , like G protein-coupled receptors, ion channels, Ca 2+ binding proteins, transcriptional networks, and ion exchangers, in both the plasma membrane and the membranes of mitochondria and endoplasmic reticulum. Interactions between Ca 2+ and reactive oxygen species signaling coordinate signaling, which can be either beneficial or detrimental. In neurodegenerative disorders, cellular Ca 2+ -regulating systems are compromised. Oxidative stress, perturbed energy metabolism, and alterations of disease-related proteins result in Ca 2+ -dependent synaptic dysfunction, impaired plasticity, and neuronal demise. We review Ca 2+ control processes relevant for physiological and pathophysiological conditions in brain tissue.

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

“…Neurocalcin is a member of the highly homologous visinin-like protein (VSNL) subfamily of neuronal calcium sensor proteins [30]; other members of this family such as VILIP-1 are reduced in the brains of Alzheimer's patients [31]. More broadly, the dysregulation of calcium homeostasis has been implicated in a range of neurodegenerative diseases via complications related to energy metabolism and oxidative stress [32,33].…”

Calretinin Expression in Hirschsprung’s Disease – A Potential Marker of Ganglion Cells

“…Whether they assume a noteworthy part as endogenous neuroprotectants is not clear. 12 In current study the mean age of the patient was 12.52±9.21 days, there were 48/73 (65.8%) cases who were ≤12 months old, 20/73 (27.4%) were 12.1-60 months old and 5/73 (6.8%) cases were 60.1-120 months old. The mean age of our patients was almost consistent with review of literature by Friedmacher et al (Friedmacher and Puri 2015).…”

“…Calcium (Ca 2+ ) manages variety of neurons , hidden learning and the memory as well as neuronal survival. 12 Calretinin, calbindin D-28, and parvalbumin have a place with a group of Ca 2+ binding proteins, which in man are more than 200. They are especially enhanced in particular cerebellar neurons.…”

Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices

“…The concept of neurotoxicity implies an excess glutamate release and/or the deficient removal of synaptic glutamate, which results in overactivation of NMDA and AMPA receptors, the cell overload with Na + and Ca 2+ , and cell death (Lau and Tymianski, 2010;Zundorf and Reiser, 2011). Hence, the neuroprotective effects of IG20 on veratridine elicited Na + and Ca 2+ overload and cell damage, prompted the experiments with glutamate.…”

“…In order to evaluate the mechanism of action involved in the neuroprotective effects of IG20 we first tested the possibility that the compound mitigated Ca 2+ overload in neurons challenged with glutamate, as Ca 2+ is linked to the neurotoxic effects of glutamate (Lau and Tymianski, 2010;Zundorf and Reiser, 2011 M) at any concentration tested (0.1 to 10 M) (see supporting information, Fig. SI3).…”