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

摘要

Abstract In previous studies, we have demonstrated the beneficial effects of classic PPARγ agonists on neuroprotection against Aβ 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 PPARγ 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 Aβ amyloid, increased expression of PGC1-1α 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. Highlights ? INT131 improves the arborization of the neuritic tree in hippocampal neurons. ? INT131 activates PPARγ and protect hippocampal neurons from Aβ-induced neurodegeneration. ? INT131 induces PGC-1α, increase mitochondrial length in hippocampal neurons. ? INT131 increases length, number and change mitochondrial morphology in CA1 region. ]]>