Neuroprotective effect of chondroitin sulfate on SH-SY5Y cells overexpressing wild-type or A53T mutant α-synuclein

Abstract

Accumulation of α-synuclein (α-SYN) is a common pathology for Parkinson's disease (PD). There is abundant evidence that the toxic-gain-of-function of α-SYN's is associated with aggregation and consequent effects. To assess the potential of chondroitin sulfate (CS) in this regard, the present study investigated its neuroprotective on SH-SY5Y cells overexpressing wild-type (WT) or A53T mutant α-SYN. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry. The protein expression levels of total α-SYN, phosphorylated Ser129 α-SYN, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cytochrome-c (Cyt-c) were analyzed by western blotting. It was observed that CS reduced the expression levels of total α-SYN and phosphorylated Ser129 α-SYN, prevented cell loss and inhibited apoptosis. The subsequent mechanism study indicated that CS inhibited ROS overproduction. CS also significantly attenuated WT and A53T mutant α-SYN-induced dysfunction, including decrease of mitochondrial membrane potential, decrease of Bcl-2 expression, and increase of Bax expression, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9, which demonstrated that CS suppressed α-SYN-induced apoptosis possibly through mitochondria protection. These results suggested that CS protects SH-SY5Y cells overexpressing WT or A53T mutant α-SYN by inhibiting the expression and phosphorylation of α-SYN, and ROS overproduction and mitochondrial apoptosis. These results implicate CS as a potential therapeutic agent for the treatment of PD.