title: Ca2+ dysregulation in the endoplasmic reticulum related to Alzheimer's disease: A review on experimental progress and computational modeling.
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.
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liang
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand. Electronic address: Don.Kulasiri@lincoln.ac.nz.
authors.forename: Don
authors.initials: D
authors.lastname: Kulasiri
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Informatics and Enabling Technologies, Lincoln University, Christchurch, New Zealand.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Samarasinghe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D019295:Computational Biology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D053763:Presenilins / Q000235:genetics / Q000378:metabolism
chemical_list: D053763:Presenilins; D002118:Calcium
keywords: Alzheimer’s disease; Amyloid-β; Ca(2+) dysregulation; Computational modeling; Endoplasmic reticulum; Systems biology