Androgen-mediated neuroprotection and its use for...

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A61K 31/568 (2006.01) A61P 25/00 (2006.01) A61P 25/28 (2006.01)

Patent

CA 2345864

~-androsten-4-OL-3.17-dione, does not prevent testosterone- Estrogen is an active neuroprotectant and is presently investi-~~ mediated neuroprotection. In contrast, anti-androgen, flutamide, gated as a potential therapy against Alzheimer's disease~~ eliminates testosterone-mediated neuroprotection. Testoster- for women. To determine if male hormones could also be~~~ one analog, methyltestosterone, showed androgen receptor- neuroprotective, we investigated the effect of testosterone,~~ dependent neuroprotection that was delayed in time indicating methyltestosterone, and epitestosterone at physiological con-~~ that a metabolite may be the active agent. The endogenous centrations on primary cultures of human neurons induced to~~ anti-androgen, epitestosterone, also showed a slight neuro- undergo apoptosis by serum deprivation. Serum deprivation~~ protective effect but not through the androgen receptor. These significantly induces neuronal apoptosis in a protracted~~ results indicate that androgens induce neuroprotection directly fashion. As expected, physiological concentrations of 17-.beta.-~ through the androgen receptor. These data suggest that andro- estradiol and transcriptionally inactive 17-.alpha.-estradiol protect~ gens may also be of therapeutic value against Alzheimer's neurons against apoptosis. Similar to 17-.beta.-estradiol, physio-~ disease in aging males. logical concentrations of testosterone are also neuroprotec- tive. Androgen receptors are present at 8 ~ 2 fmoles/mg~~~ protein in the neuron cultures. The non-aromatizable androgen,~~ mibolerone, is also neuroprotective and aromatase inhibitor,

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