Calcium and redox homeostasis in Alzheimer's disease: a focus on the endoplasmic reticulum

Abstract

Alzheimer's disease is the most frequent cause of dementia and, similarly to what is observed in other neurodegenerative disorders, neuronal dysfunction and loss is associated with alterations of proteostasis, impaired calcium homeostasis and increased accumulation of reactive oxygen species, which involve several organelles and signalling pathways. The endoplasmic reticulum is a vital organelle that plays a central role in calcium and redox homeostasis. In addition, the accumulation of abnormal proteins in the lumen of the endoplasmic reticulum induces a stress response that, depending on the stress level, activates adaptive pro-survival or deleterious pro-apoptotic pathways. Therefore, the understanding of the molecular mechanisms that regulate the balance between anti- and pro-apoptotic pathways under endoplasmic reticulum stress conditions is essential to discover novel targets for therapy in Alzheimer's disease. This review focused the role of endoplasmic reticulum stress in the deregulation of calcium and redox homeostasis during the progression of Alzheimer's disease.