Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis in Parkinson's disease models both in vitro and in vivo.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder closely associated with dopaminergic neuron loss. It is well documented that Achyranthes bidentata polypeptides (ABPP) are potent neuroprotective agents in several kinds of neurons. Therefore, we proposed that ABPP might play a beneficial role against PD by protecting dopaminergic neurons from apoptosis. SH-SY5Y cells and primary rat dopaminergic neurons were pretreated with ABPP fraction k (ABPPk), a purified fraction of ABPP, and then the cells were exposed to 1-methyl-4-phenylpyridinium iodide (MPP+ ) to induce apoptosis. Cell viability, LDH activity, a Tunel assay and protein levels of Bcl-2 and Bax were analysed. In an in vivo PD model induced by MPTP, ABPPk was intranasally delivered to mice. Behavioural tests, immunohistochemistry, immunostaining, Nissl staining, qRT-PCR and Western blot were employed to evaluate the potential effects of ABPPk on PD in mice. The application of ABPPk markedly enhanced the viability of SH-SY5Y cells and primary dopaminergic neurons treated with neurotoxic agent MPP+ . In an in vivo MPTP-induced PD model, ABPPk significantly improved behavioural performances and prevented tyrosine hydroxylase loss in the substantia nigra pars compacta and striatum. Furthermore, we showed that MPTP-induced astrocyte and microglia activation were largely attenuated by ABPPk, leading to low levels of neuroinflammation and a downregulation of the apoptotic signalling pathway. Taken together, our data show that ABPPk protects dopaminergic neurons from apoptosis, suggesting that ABPPk might be an effective intervention for treating the neuron loss associated with disorders such as PD.