Apelin-36 Mediates Neuroprotective Effects by Regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson’s Disease model mice.

Apelin-36 Mediates Neuroprotective Effects by Regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson’s Disease model mice.

Publication date: Oct 03, 2019

Parkinson’s disease (PD), a common human neurodegenerative disorder, is characterized by the presence of intraneuronal Lewy bodies composed principally of abnormal aggregated and post-translationally modified α-synuclein. In our previous research, we have demonstrated the neuroprotective effect of Apelin-36, a neuroendocrine peptide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin(MPTP)-lesioned PD model mice. Therefore, this study was designed to evaluate the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice. The results showed that MPTP-induced the depletion of dopamine in the striatum(STR) was partially reversed by Apelin-36. Apelin-36 also improved the activity of antioxidant system including superoxide dismutase (SOD) and glutathione (GSH), and decreased the overproduction of malondialdehyde (MDA) in the substantia nigra pars compacta (SNpc) and STR of MPTP-treated mice. Moreover, Apelin-36 downregulated inducible nitric oxide synthase (iNOS) and nitrated α-synuclein expression. Furthermore, Apelin-36 significantly promoted autophagy indicated by the up-regulation of LC3-II and Beclin1 and inhibition of p62 expression in the SNpc and STR of MPTP-treated mice. The protective effect of Apelin-36 was also associated with the inhibition of the apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase(JNK) signaling pathway and inactivation of caspase-3. Taken together, our findings demonstrated that the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice might be related to decreasing the aggregation of nitrated α-synuclein and alleviating oxidative stress as well as promoting autophagy and inhibiting ASK1/JNK/caspase-3 apoptotic pathway, which provides a novel strategy for PD treatment.

Zhu, J., Gao, W., Shan, X., Wang, C., Wang, H., Shao, Z., Dou, S., Jiang, Y., Wang, C., and Cheng, B. Apelin-36 Mediates Neuroprotective Effects by Regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson’s Disease model mice. 22528. 2019 Brain Res.

Concepts Keywords
Antioxidant Branches of biology
Apoptosis Programmed cell death
Apoptotic Apelin
Autophagy MPTP
Caspase 3 Autophagy
Dopamine Substantia nigra
Glutathione Parkin
INOS Neuroprotection
JNK ASK1
Kinase Neurodegeneration
Lewy Bodies Apoptosis
MDA Apoptosis
Methyl
Mice
MPTP
N Terminal
Neurodegenerative Disorder
Neuroendocrine
Neuroprotective
Neurotoxicity
Nitrated
Nitric Oxide Synthase
Overproduction
Oxidative Stress
Parkinson
Peptide
Phenyl
STR
Superoxide Dismutase

Semantics

Type Source Name
gene UNIPROT CASP3
gene UNIPROT JUN
gene UNIPROT MAP3K5
gene UNIPROT NOS2
drug DRUGBANK Nitric Oxide
drug DRUGBANK Glutathione
disease DOID SOD
drug DRUGBANK Dopamine
disease DOID neurotoxicity
gene UNIPROT SLC35G1
gene UNIPROT DESI1
disease MESH neurodegenerative disorder
pathway BSID Apoptosis
pathway BSID Oxidative Stress
disease MESH oxidative stress

Original Article

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