ANDROGEN-MEDIATED NEUROPROTECTION AND ITS USE FOR PREVENTION, TREATMENT AND STUDY OF NEURAL DISEASE

摘要

~-androsten-4-OL-3.17-dione, does not prevent testosterone-Estrogen is an active neuroprotectant and is presently investi-~~ mediatedneuroprotection. In contrast, anti-androgen, flutamide,gated as a potential therapy against Alzheimer's disease~~ eliminatestestosterone-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,~~ dependentneuroprotection that was delayed in time indicatingmethyltestosterone, and epitestosterone at physiological con-~~ that ametabolite may be the active agent. The endogenouscentrations on primary cultures of human neurons induced to~~ anti-androgen,epitestosterone, also showed a slight neuro-undergo apoptosis by serum deprivation. Serum deprivation~~ protective effectbut not through the androgen receptor. Thesesignificantly induces neuronal apoptosis in a protracted~~ results indicatethat androgens induce neuroprotection directlyfashion. As expected, physiological concentrations of 17-.beta.-~ through theandrogen receptor. These data suggest that andro-estradiol and transcriptionally inactive 17-.alpha.-estradiol protect~ gensmay also be of therapeutic value against Alzheimer'sneurons against apoptosis. Similar to 17-.beta.-estradiol, physio-~ disease inaging 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,