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Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.

Abstract
The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.
AuthorsG Cisbani, J Drouin-Ouellet, C Gibrat, M Saint-Pierre, M Lagacé, S Badrinarayanan, M H Lavallée-Bourget, J Charest, A Chabrat, L Boivin, M Lebel, M Bousquet, M Lévesque, F Cicchetti
JournalNeurobiology of disease (Neurobiol Dis) Vol. 82 Pg. 430-444 (Oct 2015) ISSN: 1095-953X [Electronic] United States
PMID26232588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antiparkinson Agents
  • Indans
  • Lipopolysaccharides
  • Neuroprotective Agents
  • rasagiline
  • Cysteamine
  • Oxidopamine
  • Cystamine
Topics
  • Animals
  • Antiparkinson Agents (pharmacology)
  • Astrocytes (drug effects, pathology, physiology)
  • Cell Line
  • Cells, Cultured
  • Corpus Striatum (drug effects, pathology, physiopathology)
  • Cystamine (pharmacology)
  • Cysteamine (pharmacology)
  • Disease Models, Animal
  • Dopaminergic Neurons (drug effects, pathology, physiology)
  • Indans (pharmacology)
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Neurites (drug effects, pathology, physiology)
  • Neuroprotective Agents (pharmacology)
  • Oxidopamine
  • Parkinsonian Disorders (drug therapy, pathology, physiopathology)

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