The Interplay between Ca(2+) Signaling Pathways and Neurodegeneration

Calcium (Ca(2+)) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca(2+) signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca(2+) concentration are needed to transmit information from neuron to neuron, between neurons and glia, and even regulating local blood flow according to the required activity. However, under pathological conditions, Ca(2+) homeostasis is altered, with increased cytoplasmic Ca(2+) concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca(2+) signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca(2+) homeostasis depends on coordinated interactions between the endoplasmic reticulum, mitochondria, and lysosomes, as well as specific transport mechanisms. In neurodegenerative diseases, alterations-increased oxidative stress, energy metabolism alterations, and protein aggregation have been identified. The aggregation of α-synuclein, β-amyloid peptide (Aβ), and huntingtin all adversely affect Ca(2+) homeostasis. Due to the mounting evidence for the relevance of Ca(2+) signaling in neuroprotection, we would focus on the expression and function of Ca(2+) signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.