کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1929324 1050452 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Impaired insulin signaling in an animal model of Niemann-Pick Type C disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Impaired insulin signaling in an animal model of Niemann-Pick Type C disease
چکیده انگلیسی

Studies have shown similarities between the histopathological characteristics of NPC and Alzheimer’s disease (AD) including amyloid and tau pathologies. While dysfunction in insulin signaling was widely detected in AD brain, the function of insulin signaling proteins has not been examined in NPC disease. In this study, we have examined the expression and phosphorylation of proteins linked to the insulin signaling pathway in the brain of 9 weeks old NPCnih mice. Our results showed lower expression of insulin receptor substrate 2 (IRS2) in the NPCnih mice, and insulin receptor substrate 1 (IRS1) expression was almost non-detectable in this NPC mouse model. This reduction was associated with the loss of expression for the regulatory p85 subunit of phosphatidylinositol 3-kinase (p85/PI3K). Interestingly, the impairment was observed to link to a greater reduction of Akt phosphorylation at residue T308 than S473. This aberrant Akt phosphorylation could be contributing to lower GSK3β phosphorylation detected in the NPCnih mouse brain. To our knowledge, this is the first report documenting impaired insulin signaling in the brain of a NPC mouse model.


► Niemann-Pick Type C disease (NPC) and Alzheimer’s disease (AD) shared several similar histopathological characteristics.
► Although insulin signaling is impaired in AD brain, the function of insulin signaling proteins in NPC is unclear.
► We detected lower IRS1 and IRS2 expression in the brain of an NPC mouse model.
► This reduction is linked to lower PI3K/Akt activity and greater GSK3β activation in the NPCnih mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 424, Issue 3, 3 August 2012, Pages 482–487
نویسندگان
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