The Interplay between Ca Signaling Pathways and Neurodegeneration.

Calcium (Ca) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca 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 homeostasis is altered, with increased cytoplasmic Ca concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca 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 homeostasis. Due to the mounting evidence for the relevance of Ca signaling in neuroprotection, we would focus on the expression and function of Ca signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.