INT131 increases dendritic arborization and protects against Aβ toxicity by inducing mitochondrial changes in hippocampal neurons

被引：9
作者：
Godoy, Juan A. [1 ,3 ]
Zolezzi, Juan M. [1 ]
Inestrosa, Nibaldo C. [1 ,2 ,3 ]
机构：
[1] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, Ctr Aging & Regenerat CARE UC, Santiago, Chile
[2] Univ New South Wales, Fac Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
[3] Univ Magallanes, Ctr Excelencia Biomed Magallanes CEBIMA, Punta Arenas, Chile
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 490卷 / 03期
关键词：
SPPARM; PPAR gamma; Amyloid-beta; Hippocampal neurons; Mitochondria; PRIMARY CORTICAL-NEURONS; ALZHEIMERS-DISEASE; AMYLOID NEURODEGENERATION; CASCADE HYPOTHESIS; GAMMA; ROSIGLITAZONE; IMPAIRMENT; ACTIVATION; SYNAPSES;
D O I：
10.1016/j.bbrc.2017.06.146
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In previous studies, we have demonstrated the beneficial effects of classic PPAR gamma agonists on neuro-protection against A beta oligomer neurotoxicity in a double transgenic mouse model of Alzheimer' disease (AD). INT-131, a novel, non-thiazolidinedione compound that belongs to a new family of drugs, selective PPAR gamma modulators (SPPARMs), has provided an emerging opportunity for the treatment of type 2 diabetes mellitus and metabolic syndrome. However, its role in the central nervous system has not been studied. The aim of this study was to evaluate the putative neuroprotective role of INT131 in hippocampal neurons. We found that INT131 increased dendritic branching, promoted neuronal survival against AD amyloid, increased expression of PGC1-1 alpha and modulated neuronal mitochondrial dynamics. Our results suggest that INT131, a drug that has been shown to be safe and effective in metabolic disorders, may constitute a new therapeutic alternative for AD. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码：955 / 962
页数：8
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