Ca2+ dysregulation in the endoplasmic reticulum related to Alzheimer's disease: A review on experimental progress and computational modeling. (August 2015)

• Record Type: Journal Article
• Authors: Liang, Jingyi; Kulasiri, Don; Samarasinghe, Sandhya
• Is Part Of: Bio systems. Volume 134(2015:Aug.)
• Page Start: 1
• Page End: 15
• Publication Date: 2015-08
• Subjects: AD Alzheimer's disease -- AICD APP intracellular domain -- APP amyloid precursor protein -- Aβ amyloid-β -- CALHM1 Ca2+ homeostasis modulator 1 -- CICR Ca2+-induced Ca2+ release -- CLI command-line interface -- DAG diacyl glycerol -- ER endoplasmic reticulum -- FAD familial AD -- GSK3β glycogen synthase kinase-3β -- GUI graphical user interface -- IBM inclusion body myositis -- IP3 inositol-1, 4, 5-trisphosphate -- IP3R inositol-1, 4, 5-trisphosphate receptor -- MAM mitochondria-associated ER membrane -- mGluR metabotropic glutamate receptor -- miRNA microRNA -- NMDAR N-methyl-d-aspartate receptor -- PIP2 phosphatidyl inositol-bisphosphate -- PLC phospholipase C -- PS presenilin -- ROS reactive oxygen species -- RyR ryanodine receptor -- SAD sporadic AD -- SERCA sarco/endoplasmic reticulum Ca2+ transport ATPase -- SOCE store-operated Ca2+ entry -- STIM stromal interaction molecule; Alzheimer's disease -- Endoplasmic reticulum -- Ca2+ dysregulation -- Amyloid-β -- Systems biology -- Computational modeling; Biological systems -- Periodicals; Biology -- Periodicals; Biology -- Periodicals; Evolution -- Periodicals; Biologie -- Périodiques; Évolution -- Périodiques; 570
• DOI: 10.1016/j.biosystems.2015.05.003
• Languages: English
• ISSNs: 0303-2647

Abstract

Abstract: Alzheimer's disease (AD) is a devastating, incurable neurodegenerative disease affecting millions of people worldwide. Dysregulation of intracellular Ca 2+ signaling has been observed as an early event prior to the presence of clinical symptoms of AD and is believed to be a crucial factor contributing to its pathogenesis. The progressive and sustaining increase in the resting level of cytosolic Ca 2+ will affect downstream activities and neural functions. This review focuses on the issues relating to the increasing Ca 2+ release from the endoplasmic reticulum (ER) observed in AD neurons. Numerous research papers have suggested that the dysregulation of ER Ca 2+ homeostasis is associated with mutations in the presenilin genes and amyloid-β oligomers. These disturbances could happen at many different points in the signaling process, directly affecting ER Ca 2+ channels or interfering with related pathways, which makes it harder to reveal the underlying mechanisms. This review paper also shows that computational modeling is a powerful tool in Ca 2+ signaling studies and discusses the progress in modeling related to Ca 2+ dysregulation in AD research.