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通过荧光共振能量转移证明活化的丝裂原活化蛋白激酶（MAP激酶）与神经原纤维缠结之间存在紧密关联：对阿尔茨海默病中MAP激酶激活的意义。

Demonstration by fluorescence resonance energy transfer of a close association between activated MAP kinase and neurofibrillary tangles: implications for MAP kinase activation in Alzheimer disease.

作者信息

Knowles R B, Chin J, Ruff C T, Hyman B T

机构信息

Alzheimer's Disease Research Unit, Massachusetts General Hospital East, Charlestown 02129, USA.

出版信息

J Neuropathol Exp Neurol. 1999 Oct;58(10):1090-8. doi: 10.1097/00005072-199910000-00007.

DOI:10.1097/00005072-199910000-00007
PMID:10515232
Abstract

Indirect evidence suggests that activation of the mitogen activated protein kinase (MAPK) cascade contributes to the hyperphosphorylation of tau found in paired helical filaments in Alzheimer disease (AD). We report colocalization of the activated form of MAPK with Ser 199/202 and Ser 396/404 phosphotau immunoreactive neurofibrillary tangles and neuritic plaques in the Alzheimer brain. Fluorescence resonance energy transfer studies (FRET) demonstrate a tight intermolecular association of activated MAPK with these phosphotau epitopes. These data support the hypothesis that activation of MAPK contributes directly to phosphorylation of tau in AD. Moreover, the stable nature of this association in postmortem human brain may suggest a stable interaction in which activated MAPK becomes tightly linked to neurofibrillary tangles.

摘要

间接证据表明，丝裂原活化蛋白激酶（MAPK）级联反应的激活导致了阿尔茨海默病（AD）中配对螺旋丝中tau蛋白的过度磷酸化。我们报告了在阿尔茨海默病大脑中，活化形式的MAPK与Ser 199/202和Ser 396/404磷酸化tau免疫反应性神经原纤维缠结和神经炎性斑块共定位。荧光共振能量转移研究（FRET）表明活化的MAPK与这些磷酸化tau表位之间存在紧密的分子间关联。这些数据支持了MAPK激活直接导致AD中tau蛋白磷酸化的假说。此外，在死后人类大脑中这种关联的稳定性可能表明存在一种稳定的相互作用，即活化的MAPK与神经原纤维缠结紧密相连。

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