Apelin-36 mitigates MPTP/MPP+-induced neurotoxicity: Involvement of α-synuclein and endoplasmic reticulum stress.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta (SNpc) which leads to the behavioral dysfunction. In the present study, we investigated the effect of Apelin-36 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)/1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. The treatment with Apelin-36 significantly alleviated the MPTP-induced the behavioral dysfunction and dopaminergic neurodegeneration in the SNpc of mice, and also remarkably decreased the MPP+-induced cell death of SH-SY5Y cells. Furthermore, Apelin-36 reversed the MPTP/MPP+-induced loss of TH expression and the induction of α-synuclein expression. Additionally, Apelin-36 significantly attenuated the endoplasmic reticulum stress (ERS) indicated by the inhibition of GRP78, CHOP and cleaved caspase-12 expression in MPTP/MPP+ treated mice and cells. Taken together, the results indicated that Apelin-36 attenuates MPTP/MPP+-induced neurotoxicity, and suggested that Apelin-36 could be a potential therapeutic strategy for the treatment of PD.