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S-propargyl-cysteine (ZYZ-802), a sulphur-containing amino acid, attenuates beta-amyloid-induced cognitive deficits and pro-inflammatory response: involvement of ERK1/2 and NF-κB pathway in rats

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Abstract

Beta-amyloid (Aβ) is considered to be responsible for the pathogenesis of Alzheimer’s disease (AD), and accumulation and aggregation of Aβ peptide in the brains of AD patients result in activation of glial cells which, in turn, initiates neuroinflammatory responses that involve reactive oxygen intermediates and release of inflammatory cytokines. In the present study, the protective effects of S-propargyl-cysteine (SPRC), also named as ZYZ-802, a sulphur-containing amino acid, on cognitive impairment and neuronal ultrastructure damage induced by Aβ were examined in rats, and the possible mechanisms were explored. These data showed that SPRC administration at the doses of 40, 80 mg/kg by intraperitoneal injection (i.p.) may inhibit cognitive impairment and neuronal ultrastructure damage induced by intracerebroventricular (i.c.v.) injection of 10 μg of Aβ25–35 in rats. Subsequently, SPRC inhibited the expressions of tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) mRNA, and protein in rat hippocampus. SPRC afforded a beneficial action on inhibitions of extracellular signal-regulated kinase (ERK1/2), as well as inhibitions of IκB-α degradation and activation of transcription factors of the nuclear factor κB (NF-κB) produced by Aβ. These findings suggested that SPRC might be a potential agent for treatment of AD.

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 Program, Grant No. 2010CB912600), National natural Science foundation of China (Grant No. 30888002) and National Drug Innovative Program (2009ZX09301-011).

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, 826 Zhang Heng Road, Shanghai, 201203, China

    Qi-Hai Gong, Li-Long Pan, Xin-Hua Liu, Qian Wang, Hui Huang & Yi-Zhun Zhu

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  1. Qi-Hai Gong
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  2. Li-Long Pan
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  3. Xin-Hua Liu
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Correspondence to Yi-Zhun Zhu.

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Gong, QH., Pan, LL., Liu, XH. et al. S-propargyl-cysteine (ZYZ-802), a sulphur-containing amino acid, attenuates beta-amyloid-induced cognitive deficits and pro-inflammatory response: involvement of ERK1/2 and NF-κB pathway in rats. Amino Acids 40, 601–610 (2011). https://doi.org/10.1007/s00726-010-0685-1

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