Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease

• Main Authors: Simona Magi, Pasqualina Castaldo, Maria Loredana Macrì, Marta Maiolino, Alessandra Matteucci, Guendalina Bastioli, Santo Gratteri, Salvatore Amoroso, Vincenzo Lariccia
• Format: Article
• Language: English
• Published: Hindawi Limited 2016-01-01
• Series: BioMed Research International
• Online Access: http://dx.doi.org/10.1155/2016/6701324

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by progressive neuronal loss. AD is associated with aberrant processing of the amyloid precursor protein, which leads to the deposition of amyloid-β plaques within the brain. Together with plaques deposition, the hyperphosphorylation of the microtubules associated protein tau and the formation of intraneuronal neurofibrillary tangles are a typical neuropathological feature in AD brains. Cellular dysfunctions involving specific subcellular compartments, such as mitochondria and endoplasmic reticulum (ER), are emerging as crucial players in the pathogenesis of AD, as well as increased oxidative stress and dysregulation of calcium homeostasis. Specifically, dysregulation of intracellular calcium homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Aberrant calcium signaling has been considered a phenomenon mainly related to the dysfunction of intracellular calcium stores, which can occur in both neuronal and nonneuronal cells. This review reports the most recent findings on cellular mechanisms involved in the pathogenesis of AD, with main focus on the control of calcium homeostasis at both cytosolic and mitochondrial level.