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

Jingyi Liang, Don Kulasiri, Sandhya Samarasinghe

Journal: Bio Systems 2016;134():1-15

PMID: 25998697

Full Text on Elsevier Science View on PubMed

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.

Address: Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.; Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand. Electronic address: [email protected].; Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Informatics and Enabling Technologies, Lincoln University, Christchurch, New Zealand.

DOI: 10.1016/j.biosystems.2015.05.003