Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons

Verkhratsky, Alexei

doi:10.1152/physrev.00004.2004

Cited by 667 publications

(631 citation statements)

References 696 publications

Supporting

Mentioning

602

Contrasting

Unclassified

Order By: Relevance

“…39,40 Recent studies have shown an involvement of ER stress and disturbed calcium homeostasis in AD. 11,39,41 Analyses of brain tissue from AD patients revealed alterations in calcium metabolism that are associated with the neurodegenerative process. Neurons containing NFT showed an increase in the levels of free and protein bound calcium compared with tangle free neuron.…”

Section: Er Stress and Admentioning

confidence: 99%

“…Neurons containing NFT showed an increase in the levels of free and protein bound calcium compared with tangle free neuron. 11,12,39 Changes in calcium may be early events in AD as shown in studies on transgenic mice expressing mutant forms of APP or PS proteins. 11,12,39 Whether elevated cell calcium is the cause or a consequence of the increase in Ab in AD remains to be investigated.…”

Section: Er Stress and Admentioning

confidence: 99%

“…2,3,10 Level of intracellular calcium and calcium release from the ER are important in ER-mitochondrial interactions and in the control of cell death ( Figure 1). 11 In the following, we will review studies on ER stress and its function in different neurodegenerative diseases by analyzing data gathered about molecular mechanisms and cellular pathways involving the ER and discuss how these cellular events may contribute to the disease process in human neurological disorders.…”

Section: Introductionmentioning

confidence: 99%

“…19 Intracellular levels of calcium are of ultimate importance for many neuronal functions including cell death. 11 The sensitivity of the mitochondria to induce cell death varies with the amounts of calcium, ROS and other metabolites present in the cell. 11,14 Apart from Bcl-2 proteins, other molecules that take part in the ER-mitochondria communications have been identified.…”

Section: Introductionmentioning

confidence: 99%

“…11 The sensitivity of the mitochondria to induce cell death varies with the amounts of calcium, ROS and other metabolites present in the cell. 11,14 Apart from Bcl-2 proteins, other molecules that take part in the ER-mitochondria communications have been identified. 2,3 Bap31 is a Bcl-2-binding transmembrane protein, important for protein trafficking.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

ER stress and neurodegenerative diseases

2006

View full text Add to dashboard Cite

show abstract

Section: Er Stress and Admentioning

confidence: 99%

Section: Er Stress and Admentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ER stress and neurodegenerative diseases

2006

View full text Add to dashboard Cite

show abstract

Genotype–phenotype correlations in Darier disease: A focus on the neuropsychiatric phenotype

Gordon‐Smith

Green

Grozeva

et al. 2018

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Darier disease (DD) is an autosomal dominant skin disorder caused by mutations in ATP2A2 encoding the sarco/endoplasmic reticulum Ca 2+ ATPase Isoform 2 (SERCA2). Evidence of a population-level association between DD and psychiatric disorders suggests that mutations in ATP2A2 may have pleiotropic effects on the brain as well as skin. Evidence of genotypephenotype relationships between ATP2A2 mutations and neuropsychiatric phenotypes would further support this suggestion. We investigated genotype-phenotype correlations between lifetime neuropsychiatric features and ATP2A2 mutation type (dichotomized into likely gene disrupting [LGD] or protein altering) in 75 unrelated individuals with DD. We also looked for evidence of clustering of mutations within SERCA2 according to neuropsychiatric features.Combining our data with the existing literature, the rate of LGD mutations was found to be significantly higher among DD cases/families with bipolar disorder, schizophrenia, or affective psychosis (p = .011). We also found a significant relationship between mutations located in the S4-M4 region of the protein and the presence of a severe neuropsychiatric phenotype (p = .032).Our findings add support to the hypothesis that Darier-causing mutations in ATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular severe psychiatric illness. This, together with evidence from research on common polymorphisms confirms ATP2A2 as a gene at which variation influences susceptibility to major psychiatric illness. K E Y W O R D SDarier disease, genotype-phenotype correlations, neuropsychiatric features

show abstract

A review of the mammalian unfolded protein response

Chakrabarti

Chen

Varner

2011

Biotech & Bioengineering

362

331

View full text Add to dashboard Cite

Proteins requiring post-translational modifications such as N-linked glycosylation are processed in the endoplasmic reticulum (ER). A diverse array of cellular stresses can lead to dysfunction of the ER and ultimately to an imbalance between protein-folding capacity and protein-folding load. Cells monitor protein folding by an inbuilt quality control system involving both the ER and the Golgi apparatus. Unfolded or misfolded proteins are tagged for degradation via ER associated degradation (ERAD) or sent back through the folding cycle. Continued accumulation of incorrectly folded proteins can also trigger the Unfolded Protein Response (UPR). In mammalian cells, UPR is a complex signaling program mediated by three ER transmembrane receptors: activating transcription factor 6 (ATF6), inositol requiring kinase 1 (IRE1) and double-stranded RNA-activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK). UPR performs three functions, adaptation, alarm and apoptosis. During adaptation, the UPR tries to reestablish folding homeostasis by inducing the expression of chaperones that enhance protein folding. Simultaneously, global translation is attenuated to reduce the ER folding load while the degradation rate of unfolded proteins is increased. If these steps fail, the UPR induces a cellular alarm and mitochondrial mediated apoptosis program. UPR malfunctions have been associated with a wide range of disease states including tumor progression, diabetes, as well as immune and inflammatory disorders. This review describes recent advances in understanding the molecular structure of UPR in mammalian cells, its functional role in cellular stress, and its pathophysiology.

show abstract

Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons

Cited by 667 publications

References 696 publications

ER stress and neurodegenerative diseases

ER stress and neurodegenerative diseases

Genotype–phenotype correlations in Darier disease: A focus on the neuropsychiatric phenotype

A review of the mammalian unfolded protein response

Contact Info

Product

Resources

About