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 (A beta) is considered to be responsible for the pathogenesis of Alzheimer's disease (AD), and accumulation and aggregation of A beta 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 A beta 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 mu g of A beta(25-35) in rats. Subsequently, SPRC inhibited the expressions of tumor necrosis factor (TNF)-alpha, 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 I kappa B-alpha degradation and activation of transcription factors of the nuclear factor kappa B (NF-kappa B) produced by A beta. These findings suggested that SPRC might be a potential agent for treatment of AD.