Role of calcium in the pathogenesis of Alzheimer's disease and transgenic models

Sub-cellular Biochemistry
Kim N GreenFrank M LaFerla

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly that is characterized by memory loss. Neuropathologically, the AD brain is marked by an increased AP burden, hyperphosphorylated tau aggregates, synaptic loss, and inflammatory responses. Disturbances in calcium homeostasis are also one of the earliest molecular changes that occur in AD patients, alongside alterations in calcium-dependent enzymes in the post-mortem brain. The sum of these studies suggests that calcium dyshomeostasis is an integral part of the pathology, either influencing AP production, mediating its effects or both. Increasing evidence from in vitro studies demonstrates that the AP peptide could modulate a number of ion channels increasing calcium influx, including voltage-gated calcium and potassium channels, the NMDA receptor, the nicotinic receptor, as well as forming its own calcium-conducting pores. In vivo evidence has shown that A3 impairs both LTP and cognition, whereas all of these ion channels cluster at the synapse and underlie synaptic transmission and hence cognition. Here we consider the evidence that AP causes cognitive deficits through altering calcium homeostasis at the synapse, thus impairing synaptic transmis...Continue Reading

Citations

Dec 18, 2015·International Journal of Molecular Medicine·Xueyuan LiRenzhi Wang
Mar 4, 2011·American Journal of Physiology. Cell Physiology·Cristina I LindeVera A Golovina
Oct 25, 2008·The Journal of Biological Chemistry·Debbi A MorrissetteFrank M LaFerla
Mar 4, 2015·Brain : a Journal of Neurology·Alaina Baker-NighChangiz Geula
Feb 10, 2018·Journal of Molecular Neuroscience : MN·Zhenning LiuKangsheng Li
Aug 2, 2013·The Journal of Biological Chemistry·William ZeigerGopal Thinakaran
Jun 14, 2012·International Journal of Cell Biology·Federica Di Sano, Mauro Piacentini
Nov 24, 2011·Journal of Pineal Research·Sergio A Rosales-CorralRussel J Reiter
Aug 5, 2009·Journal of Cellular and Molecular Medicine·Kim N Green
Oct 25, 2012·Prion·Liliana BrambillaDaniela Rossi
Jan 27, 2021·Briefings in Bioinformatics·Mengyuan YangXiaobo Zhou
Aug 1, 2008·Neuron·Kim N Green, Frank M LaFerla
Apr 9, 2011·Progress in Neurobiology·Joao P Lopes, Paula Agostinho

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