Neuroprotective actions of selective estrogen receptor modulators.
Decreasing levels of sex hormones with aging may have a negative impact on brain function, since this decrease is associated with the progression of neurodegenerative disorders, increased depressive symptoms and other psychological disturbances. Extensive evidence from animal studies indicates that sex steroids, in particular estradiol, are neuroprotective. However, the potential benefits of estradiol therapy for the brain are counterbalanced by negative, life-threatening risks in the periphery. A potential therapeutic alternative to promote neuroprotection is the use of selective estrogen receptor modulators (SERMs), which may be designed to act with tissue selectivity as estrogen receptor agonists in the brain and not in other organs. Currently available SERMs act not only with tissue selectivity, but also with cellular selectivity within the brain and differentially modulate the activation of microglia, astroglia and neurons. Finally, SERMs may promote the interaction of estrogen receptors with the neuroprotective signaling of growth factors, such as the phosphatidylinositol 3-kinase/glycogen synthase kinase 3 pathway.
DonCarlos
Lydia L
LL
Department of Cell Biology, Neurobiology and Anatomy, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA.
Azcoitia
Iñigo
I
Garcia-Segura
Luis M
LM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy; D006801:Humans; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use
D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators