Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson's disease

Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson's disease

Bourque M; Dluzen D E; Di Paolo T

Frontiers in Neuroendocrinology

2012

2012-04

Studies with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease have shown the ability of 17 beta-estradiol to protect the nigrostriatal dopaminergic system. This paper reviews the signaling pathways mediating the neuroprotective effect of 17 beta-estradiol against MPTP-induced toxicity. The mechanisms of 17 beta-estradiol action implicate activation of signaling pathways such as the phosphatidylinositol-3 kinase/Akt and the mitogen-activated protein kinase pathways. 17 beta-estradiol signaling is complex and integrates multiple interactions with signaling molecules that act to potentiate a protective effect. 17 beta-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 17 beta-estradiol. Compounds that stimulate GPER1 such as selective estrogen receptor modulators and phytoestrogens show neuroprotective activity and are alternatives to 17 beta-estradiol. (C) 2012 Published by Elsevier Inc.

Signaling; Neuroprotection; MPTP; mice; Akt; 3; 2; 1-methyl-4-phenyl-1; 6-tetrahydropyridine; receptor; Neurosciences & Neurology; Endocrinology & Metabolism; nervous-system; plasma-membrane; estrogen-receptor-alpha; er-alpha; gender-differences; rat-brain; striatum; estrogen; ERK; estradiol; growth-factor-i; protein-coupled receptor-30; selective estrogen; SERMs; Substantia nigra

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