Calcium-handling defects and neurodegenerative disease

Abstract

Calcium signaling is critical to neuronal function and regulates highly diverse processes such as gene transcription, energy production, protein handling, and synaptic structure and func-tion. Because there are many common underlying calcium-mediated pathological features observed across several neurological conditions, it has been proposed that neurodegenera-tive diseases have an upstream underlying calcium basis in their pathogenesis. With certain diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, specific sources of calcium dysregulation originating from distinct neuronal compartments or channels have been shown to have defined roles in initiating or sustaining disease mechanisms. Herein, we will review the major hallmarks of these diseases, and how they relate to calcium dysregulation. We will then discuss neuronal calcium handling throughout the neuron, with special em-phasis on channels involved in neurodegeneration.