title: 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.
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada; Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC, G1K 0A6, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Cisbani
authors.affiliation: Wallenberg Neuroscience Center, Division of Neurobiology and Lund Stem Cell Center, Lund University, BMC A11, S-221 84 Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Drouin-Ouellet
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Gibrat
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Saint-Pierre
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Lagacé
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Badrinarayanan
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: M H
authors.initials: MH
authors.lastname: Lavallée-Bourget
authors.affiliation: Centre de recherche de l'Institut Universitaire en Santé Mentale de Québec, 2601, Chemin de la Canardière, Québec, QC, G1J 2G3, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Charest
authors.affiliation: Centre de recherche de l'Institut Universitaire en Santé Mentale de Québec, 2601, Chemin de la Canardière, Québec, QC, G1J 2G3, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Chabrat
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Boivin
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Lebel
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bousquet
authors.affiliation: Centre de recherche de l'Institut Universitaire en Santé Mentale de Québec, 2601, Chemin de la Canardière, Québec, QC, G1J 2G3, Canada; Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC, G1K 0A6, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Lévesque
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada; Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC, G1K 0A6, Canada. Electronic address: Francesca.Cicchetti@crchul.ulaval.ca.
authors.forename: F
authors.initials: F
authors.lastname: Cicchetti
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003538:Cystamine / Q000494:pharmacology*; D003543:Cysteamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007189:Indans / Q000494:pharmacology; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D007189:Indans; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C031967:rasagiline; D003543:Cysteamine; D016627:Oxidopamine; D003538:Cystamine
keywords: 6-OHDA; Disease-modifying; Neuroprotection; Neurorescue