Effects of hCG on DA neuronal death of Parkinson's disease.
Biochem Biophys Res Commun
; 617(Pt 2): 41-47, 2022 08 30.
Article
em En
| MEDLINE
| ID: mdl-35689841
ABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, with the incidence in men being about twice as compared to women. Gender differences may provide clues for finding key targets that mediate the death of dopaminergic (DA) neurons in PD. Luteinizing hormone (LH), analog of human chorionic gonadotropin (hCG), and their receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), are associated with the pathogenesis of PD. Movement-related symptoms are partially improved by hCG in PD patients. However, the relationship between hCG and PD, as well as its roles in mediating DA neuronal death, has not been elucidated. In this study, we investigated the potential of hCG as a treatment during PD progression. After establishment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models, we found that hCG restored the decrease of LHCGR activity caused by down-regulation of LH in the substantia nigra. Furthermore, the reduction of LHCGR activity led to DA neuronal death through knocking down the LHCGR in DA neurons by AAV-mTH-shRNA. Treatment with hCG alleviated the DA neuronal death induced by MPTP. Finally, hCG exerted neuroprotective effects by inhibiting the activation of glycogen synthase kinase 3 beta (GSK3ß) in our MPTP-induced PD mouse and MPP+-treated SH-SY5Y cell models. Together, these results demonstrate that hCG exerts neuroprotective effects for PD through LHCGR, and the inhibition of GSK3ß activation is involved in this protective effect, suggesting that hCG can be taken as a potential therapeutic for the treatment of PD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_parkinson_disease
Assunto principal:
Doença de Parkinson
/
Fármacos Neuroprotetores
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Doenças Neurodegenerativas
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Neuroblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China