Neurosteroid and neurotransmitter alterations in Parkinson's disease

Flavia Di Michele, Sabina Luchetti, Giorgio Bernardi, Elena Romeo, Patrizia Longone

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3α, 5αtetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5α-dihydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD.

Original languageEnglish
Pages (from-to)132-142
Number of pages11
JournalFrontiers in Neuroendocrinology
Volume34
Issue number2
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Dopamine
  • GABA
  • Neurosteroids
  • Parkinson's disease

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Medicine(all)

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