Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease

Abstract

S-allyl-L-cysteine (SAC) is a sulfur-containing amino acid present in garlic and exhibits a wide range of biological activities such as antioxidant, anti-inflammatory, and anticancer agent. An earlier study demonstrated that SAC ameliorates oxidative damage in a model of experimental stroke. However, the antioxidant property of SAC does not suffice to explain its beneficial effects in terms of the underlying mechanisms. Endoplasmic reticulum (ER) stress and ER stress-induced cell death have been shown to be involved in various neurological diseases such as brain ischemia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. We have previously demonstrated that SAC exerts significant protective effects against ER stress-induced neurotoxicity in cultured rat hippocampal neurons and organotypic hippocampal slice cultures. Recently, we demonstrated that these results are due to the direct suppression of calpain activity via the binding of SAC to this enzyme's Ca²⁺-binding domain. We also found that the protective effects of the side-chain-modified SAC derivatives, S-ethyl-L-cysteine (SEC) and S-propyl-L-cysteine (SPC), against ER stress-induced neurotoxicity were more potent than those of SAC in cultured rat hippocampal neurons. In addition, SAC, SEC and SPC have been shown to decrease the production of amyloid-β peptide in the brains of mice with D-galactose-induced aging. These three hydrophilic cysteine-containing compounds have also been shown to exert neuroprotective effects against dopaminergic neuron injury in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this review, we aim to provide a current overview of the protective actions of SAC and the SAC-related compounds, SEC and SPC, in neurodegenerative disease and discuss the promise of SAC as a prototype for developing novel therapeutic drugs for neurological diseases.

Keywords: Ca2+; S-allyl-L-cysteine; calpain; cysteine-containing compounds; endoplasmic reticulum stress; neuroprotection.