Estradiol, insulin-like growth factor-I and brain aging

Luis M. Garcia-Segura, Yolanda Diz-Chaves, Margarita Perez-Martin, Muriel Darnaudéry
Psychoneuroendocrinology. 2007-08-01; 32: S57-S61
DOI: 10.1016/j.psyneuen.2007.03.001

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The decrease in some hormones with aging, such as insulin-like growth factor-I
(IGF-I) and estradiol, may have a negative impact on brain function. Estradiol
and IGF-I may antagonize the damaging effects of adrenal steroids and other
causes of brain deterioration. The signaling of estradiol and IGF-I interact to
promote neuroprotection. Estrogen receptor alpha, in an estrogen-dependent
process, can physically interact with IGF-I receptor and with the downstream
signaling molecules of the phosphotidylinositol 3-kinase (PI3K)/Akt/glycogen
synthase kinase 3 (GSK3) pathway. Estradiol and IGF-I have a synergistic effect
on the activation of Akt, which in turn decreases the activity of GSK3. This may
be one of the mechanisms used by estradiol to promote neuronal survival, since
the inhibition of GSK3 is associated to the activation of surviving signaling
pathways in neurons. Furthermore, estradiol may control Tau phosphorylation by
modulating the interactions of estrogen receptor alpha with GSK3 and
beta-catenin, another molecule involved in the regulation of neuronal survival
and the reorganization of the cytoskeleton. All these actions may be involved in
the neuroprotective effects of the hormone. Possible aging-associated changes in
the expression or activity of these signaling molecules may affect estradiol
neuroprotective effects. Therefore, it is important to determine whether aging
affects the signaling of estradiol and IGF-I in the brain.

DOI: 10.1016/j.psyneuen.2007.03.001
PMID: 17618061 [Indexed for MEDLINE]

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