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.
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 Aβ(25-35) 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.
Gong
Qi-Hai
QH
Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, 826 Zhang Heng Road, Shanghai, 201203, China.
Pan
Li-Long
LL
Liu
Xin-Hua
XH
Wang
Qian
Q
Huang
Hui
H
Zhu
Yi-Zhun
YZ
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003545:Cysteine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000276:immunology; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D003545:Cysteine