کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9879517 | 1534762 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tau pathology in Alzheimer disease and other tauopathies
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کلمات کلیدی
Neurofibrillary degeneration - دژنراسیون نوروفیبریلیالMicrotubule - ریزلوله یا میکروتوبولMemantine - ممانتین neurofilament - نوروفیلامنتProtein phosphatase-2A - پروتئین فسفاتاز 2Amicrotubule-associated protein 2 - پروتئین مرتبط با میکروتوبول 2microtubule-associated protein tau - پروتئین وابسته به میکروتوبول Tau
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Just as neuronal activity is essential to normal brain function, microtubule-associated protein tau appears to be critical to normal neuronal activity in the mammalian brain, especially in the evolutionary most advanced species, the homo sapiens. While the loss of functional tau can be compensated by the other two neuronal microtubule-associated proteins, MAP1A/MAP1B and MAP2, it is the dysfunctional, i.e., the toxic tau, which forces an affected neuron in a long and losing battle resulting in a slow but progressive retrograde neurodegeneration. It is this pathology which is characteristic of Alzheimer disease (AD) and other tauopathies. To date, the most established and the most compelling cause of dysfunctional tau in AD and other tauopathies is the abnormal hyperphosphorylation of tau. The abnormal hyperphosphorylation not only results in the loss of tau function of promoting assembly and stabilizing microtubules but also in a gain of a toxic function whereby the pathological tau sequesters normal tau, MAP1A/MAP1B and MAP2, and causes inhibition and disruption of microtubules. This toxic gain of function of the pathological tau appears to be solely due to its abnormal hyperphosphorylation because dephosphorylation converts it functionally into a normal-like state. The affected neurons battle the toxic tau both by continually synthesizing new normal tau and as well as by packaging the abnormally hyperphosphorylated tau into inert polymers, i.e., neurofibrillary tangles of paired helical filaments, twisted ribbons and straight filaments. Slowly but progressively, the affected neurons undergo a retrograde degeneration. The hyperphosphorylation of tau results both from an imbalance between the activities of tau kinases and tau phosphatases and as well as changes in tau's conformation which affect its interaction with these enzymes. A decrease in the activity of protein phosphatase-2A (PP-2A) in AD brain and certain missense mutations seen in frontotemporal dementia promotes the abnormal hyperphosphorylation of tau. Inhibition of this tau abnormality is one of the most promising therapeutic approaches to AD and other tauopathies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1739, Issues 2â3, 3 January 2005, Pages 198-210
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1739, Issues 2â3, 3 January 2005, Pages 198-210
نویسندگان
Khalid Iqbal, Alejandra del C. Alonso, She Chen, M. Omar Chohan, Ezzat El-Akkad, Cheng-Xin Gong, Sabiha Khatoon, Bin Li, Fei Liu, Abdur Rahman, Hitoshi Tanimukai, Inge Grundke-Iqbal,