Leptin reduces Alzheimer's disease-related tau phosphorylation in neuronal cells

被引：116

作者：

Greco, Steven J. ^{[1
]}

Sarkar, Sraboni ^{[1
]}

Johnston, Jane M. ^{[1
]}

Zhu, Xiongwei ^{[2
]}

Su, Bo ^{[2
]}

Casadesus, Gemma ^{[3
]}

Ashford, J. Wesson ^{[4
]}

Smith, Mark A. ^{[2
]}

Tezapsidis, Nikolaos ^{[1
]}

机构：

[1] Neurotez Inc, Bridgewater, NJ USA

[2] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA

[4] Stanford Univ, Sch Med, Stanford, CA USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 03期

关键词：

Leptin; Tau; Alzheimer's disease; Insulin; AMPK; AICAR;

D O I：

10.1016/j.bbrc.2008.09.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Leptin is a centrally acting hormone Controlling metabolic pathways. Recently, it was shown that leptin can reduce amyloid beta levels both in vitro and in vivo. Herein, phosphorylation of tau was investigated following treatment of neuronal cells with leptin and insulin. Specifically, phosphorylation of tau at amino acid residues Ser(202), Ser(396) and Ser(404) was monitored in retinoic acid induced, human cell lines: SH-SY5Y and NTera-2. Both hormones induced a concentration- and time-dependent reduction of tau Phosphorylation, and were synergistic at suboptimum concentrations. Importantly, leptin was 300-fold more potent than insulin (IC50L = 46.9 nM vs. IC50I = 13.8 mu M). A central role for AMP-dependent kinase as a mediator of leptin's action is demonstrated by the ability of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) to decrease tau phosphorylation, and by blocking leptin in the presence Of Compound C. Thus, leptin, which ameliorates both amyloid beta and tau-related pathological pathways, holds Promise as a novel therapeutic for Alzheimer's disease. (c) 2008 Elsevier Inc. All rights reserved

引用

页码：536 / 541

页数：6

共 22 条

[1]

RETINOIC ACID INDUCES NEURONAL DIFFERENTIATION OF A CLONED HUMAN EMBRYONAL CARCINOMA CELL-LINE INVITRO [J].