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Neurobiol Dis ; 82: 430-444, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26232588

RESUMO

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.


Assuntos
Antiparkinsonianos/farmacologia , Cistamina/farmacologia , Cisteamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Astrócitos/fisiologia , Linhagem Celular , Células Cultivadas , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/fisiologia , Indanos/farmacologia , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Neuritos/efeitos dos fármacos , Neuritos/patologia , Neuritos/fisiologia , Oxidopamina , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia
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