کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10765687 1050594 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice
چکیده انگلیسی
As impaired insulin signalling (IIS) is a risk factor for Alzheimer's disease we crossed mice (Tg2576) over-expressing human amyloid precursor protein (APP), with insulin receptor substrate 2 null (Irs2−/−) mice which develop insulin resistance. The resulting Tg2576/Irs2−/− animals had increased tau phosphorylation but a paradoxical amelioration of Aβ pathology. An increase of the Aβ binding protein transthyretin suggests that increased clearance of Aβ underlies the reduction in plaques. Increased tau phosphorylation correlated with reduced tau-phosphatase PP2A, despite an inhibition of the tau-kinase glycogen synthase kinase-3. Our findings demonstrate that disruption of IIS in Tg2576 mice has divergent effects on pathological processes-a reduction in aggregated Aβ but an increase in tau phosphorylation. However, as these effects are accompanied by improvement in behavioural deficits, our findings suggest a novel protective effect of disrupting IRS2 signalling in AD which may be a useful therapeutic strategy for this condition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 386, Issue 1, 14 August 2009, Pages 257-262
نویسندگان
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