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Biochem Biophys Res Commun. 2018 Jul 2;501(4):1016-1022. doi: 10.1016/j.bbrc.2018.05.101. Epub 2018 May 18.

CART peptide activates the Nrf2/HO-1 antioxidant pathway and protects hippocampal neurons in a rat model of Alzheimer's disease.

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The First Clinic Medical College, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
Queen Mary Institute, School of Medicine, Nanchang University, Nanchang, Jiangxi, 330006, China.
Department of Respiration, College of Medicine, Nanchang University, Nanchang, Jiangxi, China; Department of Respiration, Department Two, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China. Electronic address:
Department of Pathophysiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China; Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, 33006, China. Electronic address:


The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ1-42 treatment. We found that Aβ1-42 microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ1-42 and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ1-42-treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.


Alzheimer's disease (AD); Amyloid-beta (Aβ); Antioxidant; CART peptide; Nrf2; Oxidative stress

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