Repurposing sex steroids and related drugs as potential treatment for Parkinson's disease

Neuropharmacology. 2019 Mar 15:147:37-54. doi: 10.1016/j.neuropharm.2018.04.005. Epub 2018 Apr 9.

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'.

Keywords: 5-Alpha reductase inhibitor; Estrogen; Neuroprotection; Parkinson's disease; Progesterone; Selective estrogen receptor modulator.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Drug Repositioning*
  • Gonadal Steroid Hormones / therapeutic use*
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology

Substances

  • Gonadal Steroid Hormones

Grants and funding