title: Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson's disease.
abstract: Studies with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease have shown the ability of 17β-estradiol to protect the nigrostriatal dopaminergic system. This paper reviews the signaling pathways mediating the neuroprotective effect of 17β-estradiol against MPTP-induced toxicity. The mechanisms of 17β-estradiol action implicate activation of signaling pathways such as the phosphatidylinositol-3 kinase/Akt and the mitogen-activated protein kinase pathways. 17β-estradiol signaling is complex and integrates multiple interactions with signaling molecules that act to potentiate a protective effect. 17β-estradiol signaling is mediated via estrogen receptors, including GPER1, but others receptors, such as the IGF-1 receptor, are implicated in the neuroprotective effect. Glial and neuronal crosstalk is a critical factor in the maintenance of dopamine neuronal survival and in the neuroprotective action of 17β-estradiol. Compounds that stimulate GPER1 such as selective estrogen receptor modulators and phytoestrogens show neuroprotective activity and are alternatives to 17β-estradiol.
authors.affiliation: Molecular Endocrinology and Genomic Research Center, Centre de recherche du CHUQ (CHUL), Quebec City, QC, Canada G1V 4G2.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bourque
authors.forename: Dean E
authors.initials: DE
authors.lastname: Dluzen
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004967:Estrogens / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000235:genetics / Q000517:prevention & control / Q000523:psychology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
chemical_list: D004967:Estrogens; D012739:Gonadal Steroid Hormones; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine