کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6022068 | 1580662 | 2014 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons
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کلمات کلیدی
α-SynBAF-A1ANT-1FCCPAPPAβCOXMitochondrial DNA - DNA میتوکندریاMOI - MEα-synuclein - α-سینوکلینAutophagy - اتوفاژیbafilomycin A1 - بافیلومایسین A1amyloid beta - بتا آمیلوئیدFAD - بدAlzheimer's disease - بیماری آلزایمرAlzheimer's disease (AD) - بیماری آلزایمر (AD)Parkinson's disease - بیماری پارکینسونNeurodegeneration - تولید نوروژنیکMitochondrial dynamics - دینامیک میتوکندریاییmtDNA - دیانای میتوکندریاییCitrate synthase - سیترات سیتواستاتcytochrome c oxidase - سیتوکروم سی اکسیدازMicrotubules - میکروتوبول، ریزلوله هاamyloid precursor protein - پروتئین پیش ماده آمیلوئیmultiplicity of infection - چندین عفونتChloroquine - کلروکین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Functional as well as structural alterations in mitochondria size, shape and distribution are precipitating, early events in progression of Alzheimer's Disease (AD). We reported that a 20-22 kDa NH2-tau fragment (aka NH2htau), mapping between 26 and 230 amino acids of the longest human tau isoform, is detected in cellular and animal AD models and is neurotoxic in hippocampal neurons. The NH2htau -but not the physiological full-length protein- interacts with Aβ at human AD synapses and cooperates with it in inhibiting the mitochondrial ANT-1-dependent ADP/ATP exchange. Here we show that the NH2htau also adversely affects the interplay between the mitochondria dynamics and their selective autophagic clearance. Fragmentation and perinuclear mislocalization of mitochondria with smaller size and density are early found in dying NH2htau-expressing neurons. The specific effect of NH2htau on quality control of mitochondria is accompanied by (i) net reduction in their mass in correlation with a general Parkin-mediated remodeling of membrane proteome; (ii) their extensive association with LC3 and LAMP1 autophagic markers; (iii) bioenergetic deficits and (iv) in vitro synaptic pathology. These results suggest that NH2htau can compromise the mitochondrial biology thereby contributing to AD synaptic deficits not only by ANT-1 inactivation but also, indirectly, by impairing the quality control mechanism of these organelles.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 62, February 2014, Pages 489-507
Journal: Neurobiology of Disease - Volume 62, February 2014, Pages 489-507
نویسندگان
G. Amadoro, V. Corsetti, F. Florenzano, A. Atlante, M.T. Ciotti, M.P. Mongiardi, R. Bussani, V. Nicolin, S.L. Nori, M. Campanella, P. Calissano,