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CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice.
Neurol Res. 2017 Oct; 39(10):885-894.NR

Abstract

INTRODUCTION

Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1 mice.

METHODS

The protein levels of CART, soluble Aβ1-40 and Aβ1-42 were measured in the hippocampus of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1 mice using real-time PCR and western blotting. Spatial memory was measured in APP/PS1 mice using the Morris water maze. The phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting.

RESULTS

The levels of soluble Aβ1-40 and Aβ1-42 were significantly decreased in the hippocampus of APP/PS1 mice after CART treatment. CART modulated the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK pathways and activated the AKT pathway, whereas inhibition of the AKT pathway decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial memory deficits in the APP/PS1 mice.

CONCLUSION

CART decreases the levels of soluble Aβ in the hippocampus of APP/PS1 mice by modulating the expression of Aβ metabolism-associated enzymes, which may be associated with the MAPK and AKT pathways.

Authors+Show Affiliations

a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.b Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China. b Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28743230

Citation

Yin, Kailin, et al. "CART Modulates Beta-amyloid Metabolism-associated Enzymes and Attenuates Memory Deficits in APP/PS1 Mice." Neurological Research, vol. 39, no. 10, 2017, pp. 885-894.
Yin K, Jin J, Zhu X, et al. CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice. Neurol Res. 2017;39(10):885-894.
Yin, K., Jin, J., Zhu, X., Yu, L., Wang, S., Qian, L., Han, L., & Xu, Y. (2017). CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice. Neurological Research, 39(10), 885-894. https://doi.org/10.1080/01616412.2017.1348689
Yin K, et al. CART Modulates Beta-amyloid Metabolism-associated Enzymes and Attenuates Memory Deficits in APP/PS1 Mice. Neurol Res. 2017;39(10):885-894. PubMed PMID: 28743230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice. AU - Yin,Kailin, AU - Jin,Jiali, AU - Zhu,Xiaolei, AU - Yu,Linjie, AU - Wang,Sulei, AU - Qian,Lai, AU - Han,Lijuan, AU - Xu,Yun, Y1 - 2017/07/25/ PY - 2017/7/27/pubmed PY - 2018/5/16/medline PY - 2017/7/27/entrez KW - AD: Alzheimer’s disease KW - AKT pathway KW - APP: amyloid precursor protein KW - Alzheimer’s disease KW - Aβ: β-amyloid KW - CART KW - CART: Cocaine- and amphetamine-regulated transcript KW - ECE-1: endothelin-converting enzyme-1 KW - ERK: extracellular signal-regulated kinases KW - GAPDH: glyceraldehyde-3-phosphate dehydrogenase KW - IDE: insulin-degrading enzyme KW - JNK: c-Jun N-terminal kinases KW - LRP-1: low-density lipoprotein receptor-related protein 1 KW - MAPK pathways KW - MAPK: mitogen-activated protein kinase KW - NEP: neprilysin KW - RAGE: receptor for advanced glycation end products KW - beta-amyloid SP - 885 EP - 894 JF - Neurological research JO - Neurol. Res. VL - 39 IS - 10 N2 - INTRODUCTION: Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1 mice. METHODS: The protein levels of CART, soluble Aβ1-40 and Aβ1-42 were measured in the hippocampus of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1 mice using real-time PCR and western blotting. Spatial memory was measured in APP/PS1 mice using the Morris water maze. The phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting. RESULTS: The levels of soluble Aβ1-40 and Aβ1-42 were significantly decreased in the hippocampus of APP/PS1 mice after CART treatment. CART modulated the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK pathways and activated the AKT pathway, whereas inhibition of the AKT pathway decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial memory deficits in the APP/PS1 mice. CONCLUSION: CART decreases the levels of soluble Aβ in the hippocampus of APP/PS1 mice by modulating the expression of Aβ metabolism-associated enzymes, which may be associated with the MAPK and AKT pathways. SN - 1743-1328 UR - https://www.unboundmedicine.com/medline/citation/28743230/CART_modulates_beta_amyloid_metabolism_associated_enzymes_and_attenuates_memory_deficits_in_APP/PS1_mice_ L2 - http://www.tandfonline.com/doi/full/10.1080/01616412.2017.1348689 DB - PRIME DP - Unbound Medicine ER -