scholarly journals Alzheimer's genetic risk factor FERMT2 (kindlin‐2) controls axonal growth and synaptic plasticity in an APP‐dependent manner

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Fanny Eysert ◽  
AudreyAnais‐Camille CoulonVreulx ◽  
Amandine Flaig ◽  
Tiago Mendes ◽  
Benjamin Grenier‐Boley ◽  
...  
Keyword(s):  
Risk Factor ◽  
Synaptic Plasticity ◽  
Genetic Risk ◽  
Axonal Growth ◽  
Genetic Risk Factor ◽  
Dependent Manner

scholarly journals Correction to: Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2021 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Synaptic Plasticity ◽  
Genetic Risk ◽  
Axonal Growth ◽  
Genetic Risk Factor ◽  
Dependent Manner

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2019 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Large Fraction ◽  
Axonal Growth ◽  
Long Term Potentiation ◽  
Genetic Risk Factor ◽  
Dependent Manner ◽  
Genome Wide ◽  
Term Potentiation ◽  
App Metabolism

ABSTRACTAlthough APP metabolism is being intensively investigated, a large fraction of its modulators are yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a genetic risk factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance; a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism and that FERMT2 under-expression impacts axonal growth, synaptic connectivity and long-term potentiation in an APP-dependent manner. Lastly, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3’UTR of FERMT2, induced a down-regulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 under-expression in neurons and insight on how this may influence AD pathogenesis.

scholarly journals Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2020 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Large Fraction ◽  
Axonal Growth ◽  
Long Term Potentiation ◽  
Genetic Risk Factor ◽  
Dependent Manner ◽  
Genome Wide ◽  
Term Potentiation ◽  
App Metabolism

AbstractAlthough APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a genetic risk factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3′UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.

A Mutation in Plasma Platelet-activating Factor Acetylhydrolase (Val279Phe) Is a Genetic Risk Factor for Cerebral Hemorrhage but not for Hypertension

1998 ◽  
Vol 80 (09) ◽  
pp. 372-375 ◽  
Author(s):  
Hidemi Yoshida ◽  
Tadaatsu Imaizumi ◽  
Koji Fujimoto ◽  
Hiroyuki Itaya ◽  
Makoto Hiramoto ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Platelet Activating Factor ◽  
Vascular Diseases ◽  
Genetic Risk Factor ◽  
Brain Hemorrhage ◽  
Platelet Activating Factor Acetylhydrolase ◽  
Paf Acetylhydrolase ◽  
Polymerase Chain ◽  
The Difference

SummaryPlatelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.

scholarly journals 170 Psoriasis and coronary artery disease share a genetic risk factor through IFIH1

2021 ◽  
Vol 141 (5) ◽  
pp. S30
Author(s):  
M.T. Patrick ◽  
S. Sreeskandarajan ◽  
Q. Li ◽  
N. Mehta ◽  
J.E. Gudjonsson ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Genetic Risk Factor ◽  
Artery Disease
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