Effect of 5-alpha reductase inhibitors in animal models of Parkinson’s disease

Bourque, Mélanie;Morissette, Marc;Isenbrandt, Amandine;Giatti, Silvia;Cosimo Melcangi, Roberto;Carta, Manolo;Frau, Roberto;Bortolato, Marco;Soulet, Denis;Di Paolo, Thérèse

2024-01-01

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Abstract

Parkinson's disease (PD) is characterized by motor symptoms due to loss of brain dopamine and non-motor symptoms, including gastrointestinal disorders. Although there is no cure for PD, symptomatic treatments are available. L-Dopa is the gold standard PD therapy, but most patients develop dyskinesias (LID), which are challenging to manage. Amantadine is recognized as the most effective drug for LID, but its adverse effects limit the use in patients. Here we review how 5α-reductase inhibitors (5ARIs), drugs used to treat benign prostatic hyperplasia and alopecia, exhibit beneficial effects in PD animal models. 5ARIs show neuroprotective properties in brain and gut dopaminergic systems, and reduce dyskinesias in rodent model of PD. Additionally, the 5ARI finasteride dampened dopaminergic-induced drug gambling in PD patients. Neuroprotection and antidyskinetic activities of 5ARIs in animal models of PD suggest their potential repurposing in men with PD to address gut dysfunction, protect brain DA and inhibit dyskinesias.