Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells

被引：199

作者：

Greco, Steven J. ^{[1
]}

Sarkar, Sraboni ^{[1
]}

Johnston, Jane M. ^{[1
]}

Tezapsidis, Nikolaos ^{[1
]}

机构：

[1] Neurotez Inc, Res & Dev, Bridgewater, NJ 08807 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 380卷 / 01期

关键词：

Alzheimer's disease; Leptin; AICAR; beta-Amyloid; Tau; AMPK; GSK-3; beta; PPAR gamma; ACTIVATED PROTEIN-KINASE; ALZHEIMERS-DISEASE; P38; MAPK; A-BETA; CEREBRAL-CORTEX; PPAR-GAMMA; DEMENTIA; TANGLES; OBESITY; AKT;

D O I：

10.1016/j.bbrc.2009.01.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Leptin, which serves as a lipid-modulating hormone to control metabolic energy availability, is decreased in Alzheimer's disease (AD) patients, and serum levels are inversely correlated to severity of dementia. We have previously described the effects of leptin in reducing amyloid beta protein both ill vitro and in vivo, and tau phosphorylation in Vitro. Herein, we systematically investigated the signaling pathways activated by leptin, leading to these molecular endpoints, to better understand its mechanism of action. Inhibition of amyloid beta production and tau phosphorylation in leptin-treated human and/or rat neuronal cultures were both dependent on activation of AMP-activated protein kinase (AMPK). Direct stimulation of AMPK with the cell-permeable activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), replicated leptin's effects and conversely, Compound C, an inhibitor of AMPK, blocked leptin's action. The data implicate that AMPK is a key regulator of both AD-related pathways. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：98 / 104

页数：7

共 38 条

[1]

Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments [J].