scholarly journals Premature neuronal differentiation in familial Alzheimer’s disease human stem cells in vitro and in postmortem brain tissue

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Charles Arber ◽  
Christopher E.J. Lovejoy ◽  
Nanet Willumsen ◽  
Argyro Alatza ◽  
Jackie M. Casey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Stem Cells ◽  
Neuronal Differentiation ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Human Stem Cells ◽  
Familial Alzheimer’S Disease ◽  
Postmortem Brain Tissue ◽  
Familial Alzheimer's Disease

scholarly journals Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Preeti Singh ◽  
Peter S. Hanson ◽  
Christopher M. Morris
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Neural Cells ◽  
Compensatory Mechanism ◽  
Postmortem Brain Tissue ◽  
Lysine Deacetylases ◽  
Neuronal Stress

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along withα-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation ofα-synuclein aggregates but showed minimal colocalisation withα-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

scholarly journals APP Osaka Mutation in Familial Alzheimer’s Disease—Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

2020 ◽  
Vol 21 (4) ◽  
pp. 1413 ◽  
Author(s):  
Takami Tomiyama ◽  
Hiroyuki Shimada
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Synaptic Function ◽  
Recessive Inheritance ◽  
Familial Alzheimer’S Disease ◽  
Aβ Oligomers ◽  
Unique Character ◽  
Familial Alzheimer's Disease

Alzheimer’s disease is believed to begin with synaptic dysfunction caused by soluble Aβ oligomers. When this oligomer hypothesis was proposed in 2002, there was no direct evidence that Aβ oligomers actually disrupt synaptic function to cause cognitive impairment in humans. In patient brains, both soluble and insoluble Aβ species always coexist, and therefore it is difficult to determine which pathologies are caused by Aβ oligomers and which are caused by amyloid fibrils. Thus, no validity of the oligomer hypothesis was available until the Osaka mutation was discovered. This mutation, which was found in a Japanese pedigree of familial Alzheimer’s disease, is the deletion of codon 693 of APP gene, resulting in mutant Aβ lacking the 22nd glutamate. Only homozygous carriers suffer from dementia. In vitro studies revealed that this mutation has a very unique character that accelerates Aβ oligomerization but does not form amyloid fibrils. Model mice expressing this mutation demonstrated that all pathologies of Alzheimer’s disease can be induced by Aβ oligomers alone. In this review, we describe the story behind the discovery of the Osaka mutation, summarize the mutant’s phenotypes, and propose a mechanism of its recessive inheritance.

scholarly journals Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

Nature ◽  
2012 ◽  
Vol 482 (7384) ◽  
pp. 216-220 ◽  
Author(s):  
Mason A. Israel ◽  
Shauna H. Yuan ◽  
Cedric Bardy ◽  
Sol M. Reyna ◽  
Yangling Mu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
Induced Pluripotent

scholarly journals Modeling familial Alzheimer's disease with induced pluripotent stem cells

2011 ◽  
Vol 20 (23) ◽  
pp. 4530-4539 ◽  
Author(s):  
Takuya Yagi ◽  
Daisuke Ito ◽  
Yohei Okada ◽  
Wado Akamatsu ◽  
Yoshihiro Nihei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
Induced Pluripotent

Generation of induced pluripotent stem cells from a familial Alzheimer's disease patient

2011 ◽  
Vol 71 ◽  
pp. e186
Author(s):  
Naoki Yahata ◽  
Kayoko Tsukita ◽  
Yoshiko Karatsu ◽  
Fumihiko Adachi ◽  
Isao Asaka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Patient ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
Induced Pluripotent
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