The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism (Q35578655)

9 August 2017

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title

The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism (English)

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9 August 2017

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Jie Shen

1

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9 August 2017

Raymond J Kelleher

series ordinal

2

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9 August 2017

language of work or name

English

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publication date

29 December 2006

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Proceedings of the National Academy of Sciences of the United States of America

9 August 2017

published in

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9 August 2017

volume

104

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9 August 2017

issue

2

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9 August 2017

page(s)

403-409

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Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations

9 August 2017

cites work

1 reference

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Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40.

12 July 2018

1 reference

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Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms

12 July 2018

1 reference

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Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life

12 July 2018

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Presenilins in the developing, adult, and aging cerebral cortex

12 July 2018

1 reference

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Regulation of NMDA receptor trafficking by amyloid-beta

12 July 2018

1 reference

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Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios.

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Distinct mechanisms by mutant presenilin 1 and 2 leading to increased intracellular levels of amyloid beta-protein 42 in Chinese hamster ovary cells

12 July 2018

1 reference

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Amyloid beta -peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin 1 independently regulates beta-catenin stability and transcriptional activity

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

APP processing and synaptic plasticity in presenilin-1 conditional knockout mice

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Secretase targets for Alzheimer's disease: identification and therapeutic potential

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Biochemical characterization of the gamma-secretase activity that produces beta-amyloid peptides

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerability.

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A pathogenic presenilin-1 deletion causes abberrant Abeta 42 production in the absence of congophilic amyloid plaques

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Rank-order of potencies for inhibition of the secretion of abeta40 and abeta42 suggests that both are generated by a single gamma-secretase

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Calpain inhibitor I increases beta-amyloid peptide production by inhibiting the degradation of the substrate of gamma-secretase. Evidence that substrate availability limits beta-amyloid peptide production

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A substrate-based difluoro ketone selectively inhibits Alzheimer's gamma-secretase activity.

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Specific increase in amyloid beta-protein 42 secretion ratio by calpain inhibition

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Skeletal and CNS defects in Presenilin-1-deficient mice

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Assessment of normal and mutant human presenilin function in Caenorhabditis elegans

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Aspartate transcarbamylase of Escherichia coli. Mechanisms of inhibition and activation by dicarboxylic acids and other anions

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Hippocampal spatial memory impairments caused by the familial Alzheimer's disease-linked presenilin 1 M146V mutation

12 July 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Modeling clinically heterogeneous presenilin mutations with transgenic Drosophila

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and gamma-secretase activity

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Potential Link between Amyloid β-Protein 42 and C-terminal Fragment γ 49–99 of β-Amyloid Precursor Protein

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expression.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

A novel presenilin mutation (M233V) causing very early onset Alzheimer's disease with Lewy bodies.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Beta -amyloid-(1-42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival Is not compromised

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Toward the characterization and identification of gamma-secretases using transition-state analogue inhibitors.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Activated cAMP-response element-binding protein regulates neuronal expression of presenilin-1.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Abeta1-42/43 expression

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.

26 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=1766397

The carboxyl termini of beta-amyloid peptides 1-40 and 1-42 are generated by distinct gamma-secretase activities

26 September 2018

1 reference

12 December 2020

Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased A beta42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans

1 reference

12 December 2020

Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation

1 reference

12 December 2020

Peptidomimetic probes and molecular modeling suggest that Alzheimer's gamma-secretase is an intramembrane-cleaving aspartyl protease

1 reference

12 December 2020

Identifiers

DOI

10.1073/PNAS.0608332104

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9 August 2017

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9 August 2017

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