کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8303603 | 1537943 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modeling endophilin-mediated Aβ disposal in glioma cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
miR34aPCCwide-typeAβGEOCtsBLC3amyloid-β - آمیلوئید βAutophagy - اتوفاژیAlzheimer disease - بیماری آلزایمرELISA - تست الیزاPearson correlation coefficient - ضریب همبستگی پیرسونMass spectrometry - طیف سنجی جرمیUTR یا untranslated regions - منطقه ترجمه نشدهuntranslated region - منطقه غیر ترجمهGene ontology - هستیشناسی ژنیhemagglutinin - هماگلوتینینWestern blot - وسترن بلاتmicrotubule-associated protein 1A/1B-light chain 3 - پروتئین پروتئین 1A / 1B مرتبط با میکروتوبول زنجیره 3Gene Expression Omnibus - ژن بیان OmnibusCathepsin B - کاتئفسین B
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Modeling endophilin-mediated Aβ disposal in glioma cells Modeling endophilin-mediated Aβ disposal in glioma cells](/preview/png/8303603.png)
چکیده انگلیسی
Autophagy dysregulation has emerged in age-related neurological diseases (Ulland et al.; Matheoud et al.; Ashkenazi et al.). Alzheimer Disease (AD), the most common progressive neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) plaques caused by aberrant Aβ metabolism (Qiang et al.; Sevigny et al.; Ittner et al.). Glia constitute the brain immune system and ingest extracellular Aβ for degradation via the autophagy-lysosome machinery (Ries and Sastre; Cho et al.). Here, we model the molecular rationale for this clearance process in glioma cells by showing that miR34a inhibits autophagy-mediated disposal of Aβ fibrils and identifying two novel direct targets of miR34a, endophilin-3 and cathepsin B (CTSB, a previously reported enzyme for Aβ degrading (Sun et al.)). Bioinformatics analyses revealed that endophilin-3 expresses at a significantly lower level in neurodegenerative diseases. Its gain-of-function substantially promotes both uptake and degradation of Aβ while small interfering RNA (siRNA)-mediated endophilin-3 knockdown slowed down Aβ clearance and blocked autolysosome formation. Mechanistically, gene ontology (GO) analysis of the endophilin-3 interactome identified by mass spectrometry uncovered enriched components involved in actin binding (with the highest score). Importantly, we validated that the actin-binding protein phostensin interacted with endophilin-3. Phostensin knockdown restored endophilin-3-mediated up-regulation of Aβ clearance. Thus, our findings indicate that miR34a inhibits Aβ clearance by targeting endophilin-3 and CTSB at multiple steps including uptake and autophagy-mediated degradation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1865, Issue 10, October 2018, Pages 1385-1396
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1865, Issue 10, October 2018, Pages 1385-1396
نویسندگان
Bing Sun, Ping Fan, Meijian Liao, Yaou Zhang,