کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6809174 | 1433595 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aβ-induced formation of autophagosomes is mediated by RAGE-CaMKKβ-AMPK signaling
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Pathological autophagic vacuoles (AVs) accumulate in the brains of Alzheimer's disease (AD) patients, but the mechanisms by which they are induced are unknown. In this study, we found that the formation of AVs was mediated by activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the brains of APP/PS1 double transgenic mice, amyloid-beta peptide (Aβ) pathology-bearing model mouse. Injection of sunitinib malate, AMPK inhibitor, to the mice lowered AV formation in their brains. Consistent with our in vivo observations, treatment of SH-SY5Y cells with Aβ enhanced the induction of autophagosomes, which was mediated by Ca2+/calmodulin-dependent protein kinase kinase-beta (CaMKKβ)-AMPK signaling, as shown using various inhibitors and small interfering RNA (siRNA). CaMKKβ is a calcium-activated kinase, and the depletion of intracellular calcium by BAPTA-AM, a Ca2+ chelator, also curtailed Aβ-induced autophagy. Finally, the inhibition of receptor for advanced glycation end products (RAGE) attenuated autophagsome formation and AMPK signaling. Conversely, RAGE overexpression amplified the induction of autophagy. These results implicate the regulation of the Aβ-induced formation of AVs by the RAGE-calcium-CaMKKβ-AMPK pathway and suggest that modulation of autophagosome formation and the interaction between Aβ and RAGE are beneficial in the treatment and prevention of Alzheimer's disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 33, Issue 5, May 2012, Pages 1006.e11-1006.e23
Journal: Neurobiology of Aging - Volume 33, Issue 5, May 2012, Pages 1006.e11-1006.e23
نویسندگان
Sung Min Son, Eun Sun Jung, Hong Joon Shin, Jayoung Byun, Inhee Mook-Jung,