Neuroprotective actions of sex steroids in Parkinson's disease.
The sex difference in Parkinson's disease, with a higher susceptibility in men, suggests a modulatory effect of sex steroids in the brain. Numerous studies highlight that sex steroids have neuroprotective properties against various brain injuries. This paper reviews the protective effects of sex hormones, particularly estradiol, progesterone and androgens, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease as compared to methamphetamine toxicity. The molecular mechanisms underlying beneficial actions of sex steroids on the brain have been investigated showing steroid, dose, timing and duration specificities and presently focus is on the dopamine signaling pathways, the next frontier. Both genomic and non-genomic actions of estrogen converge to promote survival factors and show sex differences. Neuroprotection by estrogen involves activation of signaling molecules such as the phosphatidylinositol-3 kinase/Akt and the mitogen-activated protein kinase pathways. Interaction with growth factors, such as insulin-like growth factor 1, also contributes to protective actions of estrogen.
Bourque
Mélanie
M
Molecular Endocrinology and Genomic Research Center, Laval University Medical Center, CHUL, Quebec City, Quebec, Canada.
Dluzen
Dean E
DE
Di Paolo
Thérèse
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D004967:Estrogens / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology; D013256:Steroids / Q000378:metabolism / Q000627:therapeutic use*
D015259:Dopamine Agents; D004967:Estrogens; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D013256:Steroids; D008694:Methamphetamine; D011374:Progesterone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine