Cytosolic Abnormally Hyperphosphorylated Tau But Not Paired Helical Filaments Sequester Normal MAPs and Inhibit Microtubule Assembly
作者： Khalid Iqbal , Alejandra del C. Alonso , Inge Grundke-Iqbal
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摘要: Neurofibrillary degeneration of abnormally hyperphosphorylated tau, a hallmark Alzheimer's disease (AD) and related tauopathies, occurs both as cytosolic aggregated/oligomeric protein (AD P-tau) neurofibrillary tangles. The abnormal hyperphosphorylation not only results in the loss tau function promoting assembly stabilizing microtubules but, case AD P-tau, also gain toxic whereby pathological sequesters normal but other two neuronal microtubule associated proteins (MAPs), MAP1A / MAP1B MAP2, causes inhibition disruption microtubules. sequestration MAPs leads to slow progressive affected neurons. neurons defend against by continually synthesizing new well packaging into polymers, i.e., tangles paired helical filaments, twisted ribbons straight filaments. filamentous is inert; it neither interacts with tubulin stimulates assembly, nor binds These findings suggest aggregation preferred therapeutic target for tauopathies.
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