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IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.
Am J Physiol Endocrinol Metab. 2020 10 01; 319(4):E734-E743.AJ

Abstract

Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP+) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.

Authors+Show Affiliations

Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, School of Basic Medicine, Qingdao University, Qingdao, China. School of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China.Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32865008

Citation

Wang, Xiao-Wen, et al. "IGF-1 Inhibits MPTP/MPP+-induced Autophagy On Dopaminergic Neurons Through the IGF-1R/PI3K-Akt-mTOR Pathway and GPER." American Journal of Physiology. Endocrinology and Metabolism, vol. 319, no. 4, 2020, pp. E734-E743.
Wang XW, Yuan LJ, Yang Y, et al. IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER. Am J Physiol Endocrinol Metab. 2020;319(4):E734-E743.
Wang, X. W., Yuan, L. J., Yang, Y., Zhang, M., & Chen, W. F. (2020). IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER. American Journal of Physiology. Endocrinology and Metabolism, 319(4), E734-E743. https://doi.org/10.1152/ajpendo.00071.2020
Wang XW, et al. IGF-1 Inhibits MPTP/MPP+-induced Autophagy On Dopaminergic Neurons Through the IGF-1R/PI3K-Akt-mTOR Pathway and GPER. Am J Physiol Endocrinol Metab. 2020 10 1;319(4):E734-E743. PubMed PMID: 32865008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER. AU - Wang,Xiao-Wen, AU - Yuan,Liang-Jie, AU - Yang,Ye, AU - Zhang,Mei, AU - Chen,Wen-Fang, Y1 - 2020/08/31/ PY - 2020/9/1/pubmed PY - 2021/1/1/medline PY - 2020/9/1/entrez KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - G protein-coupled estrogen receptor KW - Parkinson’s disease KW - autophagy KW - insulin-like growth factor-1 SP - E734 EP - E743 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 319 IS - 4 N2 - Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP+) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/32865008/IGF_1_inhibits_MPTP/MPP+_induced_autophagy_on_dopaminergic_neurons_through_the_IGF_1R/PI3K_Akt_mTOR_pathway_and_GPER_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00071.2020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -