Grant: Travel Awards - Institute Community Support

Parkinson's disease (PD) is a progressive brain disease characterized by a loss of dopamine-producing cells responsible for body movement. There is no cure for PD; treatments available treat only the symptoms while they induce motor complications after years of treatment. Our research is developing protective therapies that can stop the progression of the disease. PD is reported to affect more men than women. While hormones produced by ovaries like estradiol and progesterone exhibit neuroprotection of the dopamine-producing cells, hormones produced by testis as testosterone have shown no beneficial effects. Dihydrotestosterone (DHT), a more potent male hormone, is transformed from testosterone by 5alpha-reductase enzymes and, thus, a potential therapeutic benefit could be achieved through the inhibition of these enzymes. In this project, we advance the hypothesis that inhibition of 5alpha-reductases by dutasteride results in reduction of DHT production and enhancement of testosterone concentration. Testosterone could thus be transformed in estradiol. The inhibition of 5alpha-reductase inhibit progesterone metabolism and elevate progesterone concentration. Intact mice and mice exposed to MPTP that mimics PD were treated with dutasteride. Dutasteride protected the dopamine-producing cells by preventing the adverse effects of MPTP on the dopamine synthesis and on the expression of two transporters of dopamine (DAT and VMAT2) that play important roles in the release and transport of dopamine among brain cells. Furthermore, dutasteride enhanced the expression of the transporter DAT in intact mice. These results suggest that the inhibition of 5alpha-reductase by dutasteride promote the protection of dopaminergic cells. Modulation of hormone production represents a potential target for treatment strategies to slow the disease progression.