Protective effects of s-propargylcysteine (SPRC) on in vitro neuronal damage induced by Amyloid-Beta (25-35)

WONG WAN HUI

Publication

Protective effects of s-propargylcysteine (SPRC) on in vitro neuronal damage induced by Amyloid-Beta (25-35)

WONG WAN HUI

Abstract

Alzheimer?s disease (AD) is a neurodegenerative disease characterized by widespread extracellular deposits of amyloid-beta (A?) protein in the brain. Amongst which, the A?25-35 peptide is the shortest fragment which retains the toxicity of the full-length protein. In this study, this peptide was found to aggregate in a time- and temperature-dependent manner. This aggregation can be slowed with the co-incubation of S-propargyl-cysteine (SPRC), S-allyl-cysteine (SAC) or sodium hydrosulfide (NaHS) in the solution, accompanied with decreased sizes of the A? aggregates. A? radicalizes in solution to cause detrimental damage even outside cells. SPRC can scavenge free radicals better than SAC, but less competent than NaHS. The triple bond in SPRC is more nucleophilic than SAC that can react with the lone pair of electrons in free radicals. Oligomeric or fibrillar A?25-35 were added to the C6 glioma cell line and the cell viabilities were compromised. The decline in cell viability was more obvious when treated with fibrillar A?25-35, which acted on exacerbating oxidative stress by increasing H2O2 levels, inflammation and disruption of the autophagic activation. Moreover, the aggregated A? decreased the H2S levels produced and the expression of cystathione-? synthase (CBS) in the cells. Pre-treatments of SPRC and SAC both restored the A?-induced reductions in cell viabilities, but the doses required to restore the cell viabilities were higher in damage by A? fibrils. SPRC mimicked the protection by SAC on glioma cells through its antioxidant nature, particularly targeting superoxide dismutase (SOD) and glutathione peroxidase (GPx) in both forms of A? injuries. SPRC also decreases pro-inflammatory IL-1? and increases anti-inflammatory IL-10 to reduce the inflammatory responses evoked by A?25-35 though differently from SAC. SPRC reduces DNA fragmentation and reverses autophagic activation that preserves cellular integrity in a similar manner to SAC. These protective effects of SPRC can be due its cysteine backbone similar to SAC and its endogenous H2S-producing nature. When compared to NaHS that produces H2S exogenously, SPRC sustains the protection to the cellular status despite the form of A?. These promising results can suggest SPRC as a novel therapeutic agent for neurodegenerative diseases.