Calcium (Ca²⁺) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca²⁺ signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca²⁺ 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, Ca²⁺ homeostasis is altered, with increased cytoplasmic Ca²⁺ concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca²⁺ signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca²⁺ 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 Ca²⁺ homeostasis. Due to the mounting evidence for the relevance of Ca²⁺ signaling in neuroprotection, we would focus on the expression and function of Ca²⁺ signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.