Protein phosphatases and Alzheimer's disease.
Protein phosphatases and Alzheimer's disease.
复制标题
蛋白质磷酸酶和阿尔茨海默氏病。
DOI：
10.1016/b978-0-12-396456-4.00012-2
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发表时间：
2012
影响因子：
--
通讯作者：
Nairn, Angus C.
中科院分区：
文献类型：
--
作者：
Braithwaite, Steven P.;Stock, Jeffry B.;Lombroso, Paul J.;Nairn, Angus C.
阿尔茨海默病（AD）的特点是认知功能的进行性丧失，与显著的神经元丧失有关。该疾病的病理特征是淀粉样蛋白-β (Aβ)肽以淀粉样斑块的形式积累和细胞内神经原纤维缠结（nft）的形成。越来越多的证据表明，蛋白磷酸化在a β的正常和病理作用以及nft的形成中都起着关键作用。nft含有微管结合蛋白tau的过度磷酸化形式，并且几种不同激酶的tau磷酸化导致其聚集。参与产生和/或作用tau或Aβ的蛋白激酶是预防或减轻AD病理的可行药物靶点。然而，人们也认识到，逆转这些蛋白激酶作用的蛋白磷酸酶同样重要。在这里，我们回顾了我们对丝氨酸/苏氨酸和酪氨酸蛋白磷酸酶在AD病理中的理解的最新进展。
Alzheimer’s Disease (AD) is characterized by progressive loss of cognitive function, linked to marked neuronal loss. Pathological hallmarks of the disease are the accumulation of the amyloid-β (Aβ) peptide in the form of amyloid plaques and the intracellular formation of neurofibrillary tangles (NFTs). Accumulating evidence supports a key role for protein phosphorylation in both the normal and pathological actions of Aβ as well as the formation of NFTs. NFTs contain hyperphosphorylated forms of the microtubule-binding protein tau, and phosphorylation of tau by several different kinases leads to its aggregation. The protein kinases involved in the generation and/or actions of tau or Aβ are viable drug targets to prevent or alleviate AD pathology. However, it has also been recognized that the protein phosphatases that reverse the actions of these protein kinases are equally important. Here, we review recent advances in our understanding of serine/threonine and tyrosine protein phosphatases in the pathology of AD.