The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons

被引：1
作者：
Guha, Isa [1 ,2 ]
Slamova, Ivana [1 ,2 ]
Chun, Soyon [1 ,2 ]
Clegg, Arthur [1 ,2 ]
Golos, Michal [1 ,2 ]
Thrasivoulou, Chris [3 ]
Simons, J. Paul [1 ,2 ]
Al-Shawi, Raya [1 ,2 ]
机构：
[1] UCL, Ctr Amyloidosis & Acute Phase Prot, Div Med, Genet Unit, Royal Free Campus, London, England
[2] UCL, Ctr Amyloidosis & Acute Phase Prot, Div Med, Wolfson Drug Discovery Unit, Royal Free Campus, London, England
[3] UCL, Res Dept Cell & Dev Biol, London, England
来源：
NEUROBIOLOGY OF AGING | 2016年 / 46卷
基金：
英国国家替代、减少和改良动物研究中心; 英国惠康基金;
关键词：
Aging; JNK; Neurons; NGF; ProNGF; NRAGE; P75 NEUROTROPHIN RECEPTOR; C-JUN; CELL-DEATH; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; PC12; CELLS; AXONAL REGENERATION; MEDIATED APOPTOSIS; CORTICAL-NEURONS; BASAL FOREBRAIN;
D O I：
10.1016/j.neurobiolaging.2016.06.016
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
During the course of normal aging, certain populations of nerve growth factor (NGF)-responsive neurons become selectively vulnerable to cell death. Studies using dissociated neurons isolated from neonates have shown that c-Jun N-terminal kinases (JNKs) are important in regulating the survival and neurite outgrowth of NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic neurons are not dependent on NGF for their survival. Moreover, the NGF precursor, proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons. Because of these age-related differences, the effects of JNK inhibition on the survival and growth of sympathetic neurons isolated from aged mice were studied. Aged neurons, as well as glia, were found to be dependent on JNK for their growth but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was independent of NRAGE. These results have implications for the potential use of JNK inhibitors as therapies for ameliorating age-related neurodegenerative disease. (C) 2016 Elsevier Inc. All rights reserved.
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页码：138 / 148
页数：11
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