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Curcumin Alleviates Aβ42-Induced Neuronal Metabolic Dysfunction via the Thrb/SIRT3 Axis and Improves Cognition in APPTG Mice

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Abstract

Curcumin has been reported to have a therapeutic effect on Alzheimer’s disease (AD), but the specific mechanism remains to be elucidated. In the present research, we aimed to investigate the effect and molecular mechanism of curcumin on AD. Mouse primary hippocampal neuron cells were treated with various concentrations of beta-amyloid 42 (Aβ42) and the results found that Aβ42 inhibited cell viability in a dose-dependent manner. Compared with 50 ng/mL Aβ42, 500 ng/mL Aβ42 could further promote cell apoptosis, reduce the ratio of Nicotinamide adenine dinucleotide (NAD(+))/Nicotinamide adenine diphosphate hydride (NADH) and Adenosine 5′-triphosphate (ATP) level, and inhibit Sirtuins 3 (SIRT3) deacetylation activity and protein expression of Thyroid hormone receptor beta (Thrb) and SIRT3. Hence, 500 ng/mL Aβ42 was used to establish a cell model of AD. Curcumin significantly reversed the inhibitory effects of Aβ42 on cell viability, SIRT3 deacetylation activity, the ratio of NAD+/NADH, ATP level and the protein expression of Thrb and SIRT3, and the promotive effect on apoptosis. ChIPBase was used to predict the binding region of Thrb and SIRT3. Dual luciferase reporter gene and Chromatin immune precipitation (ChIP) assays were employed to verify the relationship between Thrb and promoter of SIRT3 mRNA. Overexpression of Thrb recovered Aβ42 induced metabolic dysfunction, while Thrb silence aggravated Aβ42 induced metabolic dysfunction. Moreover, Thrb silence or 3-TYP (a selective inhibitor of SIRT3) treatment abolished the amelioration of curcumin on Aβ42 induced metabolic dysfunction. Additionally, curcumin attenuated memory deficits in Amyloid precursor protein transgenic (APPTG) mice. Collectively, curcumin alleviated Aβ42-induced neuronal metabolic dysfunction through increasing Thrb expression and SIRT3 activity and improved cognition in APPTG mice.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Basic Disciplines, Jiangxi Health Vocational College, Nanchang, 330052, China

    Min Liu & Xiaodan Zhang

  2. Department of Recuperation No.1, Dalian Rehabilitation and Recuperation Center, Dalian, 116016, China

    Ying Wang

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Liu, M., Zhang, X. & Wang, Y. Curcumin Alleviates Aβ42-Induced Neuronal Metabolic Dysfunction via the Thrb/SIRT3 Axis and Improves Cognition in APPTG Mice. Neurochem Res 46, 3166–3178 (2021). https://doi.org/10.1007/s11064-021-03414-x

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