کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4330090 | 1614241 | 2008 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phosphorylation of β-amyloid precursor protein (APP) cytoplasmic tail facilitates amyloidogenic processing during apoptosis
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Secretion and progressive cerebral accumulation of β-amyloid peptides (Aβ) derived by endoproteolytic (“amyloidogenic”) processing of β-amyloid precursor protein (APP) represent collectively an early and necessary event in the pathogenesis of Alzheimer's disease. We previously demonstrated that secretion of the neurotoxic species Aβ42 increases during staurosporine-induced apoptosis in undifferentiated PC12 cells, in an endocytosis-dependent manner. In the present study, we tested whether phosphorylation of the APP cytoplasmic-tail is contributory to this apoptosis-related increased Aβ-secretory response. We demonstrate that cytoplasmic-tail phosphorylation specifically at amino-acid residue T668 (APP-695 numbering) increases during staurosporine-induced apoptosis, in parallel with activation of the mitogen-activated, proline-directed serine/threonine protein kinase ERK1. We demonstrate additionally that specific ERK inhibition during staurosporine induction, with serum-free conditions, results in down-regulation of APP phosphorylation at T668, together with attenuation of the increased Aβ-secretory response. These results are consistent with APP cytoplasmic-tail phosphorylation at T668 during apoptosis as contributory to increased Aβ42 secretion originating from the endocytotic pathway, likely with cell-line restriction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1198, 10 March 2008, Pages 204-212
Journal: Brain Research - Volume 1198, 10 March 2008, Pages 204-212
نویسندگان
Chhinder P. Sodhi, Ruth G. Perez, Numa R. Gottardi-Littell,