Repurposing sex steroids and related drugs as potential treatment for Parkinson's disease. (15th March 2019)

• Record Type: Journal Article
• Authors: Bourque, Mélanie; Morissette, Marc; Di Paolo, Thérèse
• Is Part Of: Neuropharmacology. Volume 147(2019)
• Page Start: 37
• Page End: 54
• Publication Date: 2019-03-15
• Subjects: Estrogen -- Progesterone -- Selective estrogen receptor modulator -- 5-Alpha reductase inhibitor -- Neuroprotection -- Parkinson's disease; DA dopamine -- DHEA dehydroepiandrosterone -- GFAP glial fibrillary acidic protein -- l-DOPA L-3, 4-dihydroxyphenylalanine -- MPP+ 1-methyl-4-phenylpyridium -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- PD Parkinson's disease -- SERM selective estrogen receptor modulators -- 6-OHDA 6-hydroxydopamine; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.04.005
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder for which a greater prevalence and incidence is described in men. This suggests a protective effect of sex hormones in the brain. Therefore, steroids and drugs to treat endocrine conditions could have additional application for PD. Here, we review the protective effect of sex hormones, particularly estrogens, progesterone, androgens and dehydroepiandrosterone, in animal models of PD and also in human studies. Data also support that drugs affecting estrogen neurotransmission such as selective estrogen receptor modulators or affecting steroid metabolism with 5α-reductase inhibitors could be repositioned for treatment of PD. Sex steroids are also modulator of neurotransmission, thus they could repurposed to treat PD motor symptoms and to modulate the response to PD medication. No drug is yet available to limit PD progression. PD is a complex disease implicating multiple pathological processes and a therapeutic strategy using drugs with several mechanisms of action, such as sex steroids and endocrine drugs are interesting repositioning options for symptomatic treatment and disease-modifying activity for PD. This article is part of the Special Issue entitled 'Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders'. Highlights: Exposure to estrogens is associated with a lower risk to develop PD. Estradiol, progesterone, DHEA and raloxifene are protective in animal models of PD. Progesterone has rescue activity in animal models of PD. Neurosteroids modulate PD motor symptoms and dyskinesia. The 5α-reductase inhibitor dutasteride is neuroprotective.