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%A LI Li-xuan, LI Xiao-hui %T The Mechanisms and Research Progress of Tau Abnormality Leading to AD Related Neurodegenerative Taupathies %0 Journal Article %D 2011 %J ACTA NEUROPHARMACOLOGICA %R %P 34-39 %V 1 %N 5 %U {http://actanp.hebeinu.edu.cn/CN/abstract/article_49.shtml} %8 2011-10-26 %X Tau, as a neuronally specific microtubule associated protein, plays a key role in promoting tubulin associated microtubule assembly, sustaining normal neuron axonal transport and stabilizing microtubule structure. Previous studies in autopsy revealed a tangible parallel relationship of brain neurofibrillary tangles (NFTs) to neurodegeneration, cell dysmorphology and apoptosis, thus leading to the consensus of NFTs being the major pathogenic factor in neurodegenerative taupathies, which are related to tau protein hyperphosphorylation. However, recent discoveries showed that Tau phosphorylation alone is insufficient for the formation of NFTs; other post-translational modifications such as glycosylation, proline isomerization, ubiquitination, as well as tau gene mutation and autophagy inhibition, are also required. In particular, recent researches using transgenic animals and multiphoton imaging technology indicated that NFTs seem to be just one clinical manifestation at the advanced stage of this disease, whereas soluble Tau protein plays an important role in initiating downstream pathological processes. Remarkably, suppression of Tau prohibited Aβ induced neuronal apoptosis and reduced memory impairment, suggesting that Aβ toxicity is Tau protein dependent. Along with the recent new light shed on the Tau abnormality induced neurodegenerative taupathies and its mechanism, Aβ as a drug target proved to be a failure in the field of drug discovery. As a result increasing attention has been given to tau targeted drug development.