Neuroprotective effects of osmotin in Parkinson’s disease-associated pathology via the AdipoR1/MAPK/AMPK/mTOR signaling pathways

Journal of Biomedical Science

Research

Jun Sung Park¹  Hyeon Jin Lee¹  Myeong Ok Kim²  Kyonghwan Choe³  Tae Ju Park⁴ 

[1] Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, 52828, Jinju, Republic of Korea;Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, 52828, Jinju, Republic of Korea;Alz-Dementia Korea Co., 52828, Jinju, Republic of Korea;Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, 52828, Jinju, Republic of Korea;Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229ER, Maastricht, the Netherlands;Haemato-Oncology/Systems Medicine Group, Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences (MVLS), University of Glasgow, G12 0ZD, Glasgow, UK;

关键词: Parkinson’s disease;    Osmotin;    α-Synuclein;    Dopaminergic neuron;    Neuroinflammation;   

DOI  :  10.1186/s12929-023-00961-z

 received in 2023-05-02, accepted in 2023-08-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundParkinson’s disease (PD) is the second most frequent age-related neurodegenerative disorder and is characterized by the loss of dopaminergic neurons. Both environmental and genetic aspects are involved in the pathogenesis of PD. Osmotin is a structural and functional homolog of adiponectin, which regulates the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK) via adiponectin receptor 1 (AdipoR1), thus attenuating PD-associated pathology. Therefore, the current study investigated the neuroprotective effects of osmotin using in vitro and in vivo models of PD.MethodsThe study used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and neuron-specific enolase promoter human alpha-synuclein (NSE-hαSyn) transgenic mouse models and 1-methyl-4-phenylpyridinium (MPP+)- or alpha-synuclein A53T-treated cell models. MPTP was injected at a dose of 30 mg/kg/day for five days, and osmotin was injected twice a week at a dose of 15 mg/kg for five weeks. We performed behavioral tests and analyzed the biochemical and molecular changes in the substantia nigra pars compacta (SNpc) and the striatum.ResultsBased on our study, osmotin mitigated MPTP- and α-synuclein-induced motor dysfunction by upregulating the nuclear receptor-related 1 protein (Nurr1) transcription factor and its downstream markers tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2). From a pathological perspective, osmotin ameliorated neuronal cell death and neuroinflammation by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, osmotin alleviated the accumulation of α-synuclein by promoting the AMPK/mammalian target of rapamycin (mTOR) autophagy signaling pathway. Finally, in nonmotor symptoms of PD, such as cognitive deficits, osmotin restored synaptic deficits, thereby improving cognitive impairment in MPTP- and α-synuclein-induced mice.ConclusionsTherefore, our findings indicated that osmotin significantly rescued MPTP/α-synuclein-mediated PD neuropathology. Altogether, these results suggest that osmotin has potential neuroprotective effects in PD neuropathology and may provide opportunities to develop novel therapeutic interventions for the treatment of PD.

【 授权许可】

CC BY   
© National Science Council of the Republic of China (Taiwan) 2023

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