Abstract
Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons located in the substantia nigra (SN). Data from our group and others indicate that metals, oxidative stress, and bioavailable reductants provide a possible mechanism for the neurodegeneration observed in PD. 6-Hydroxydopamine (6-OHDA) injection into the nigra of mice resulted in quantified loss of dopaminergic neurons. Oral administration of the metal–protein binding compound clioquinol (CQ) commencing on the day of lesion led to a significant reduction in lesion size. This finding elaborates upon our previous study that long-term pre-treatment with CQ reduced the susceptibility of SN neurons to another neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrapyridine (MPTP) (Kaur et al. 2003), suggesting metals as a common pathway for propagation of these lesions. Human neuroblastoma M17 cells were susceptible to metal, 6-OHDA and dopamine-induced cell death that was partially recoverable by co-incubation with CQ or catalase. These results support the concept that CQ or a similar moderate-affinity transition metal ligand could modulate neuronal oxidative stress and therefore may be a novel class of drug that may be useful for the treatment of PD.
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This study was funded by Prana Biotechnology Ltd., Australian Brain Foundation as well as funds from the National Health and Medical Research Council.
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Wilkins, S., Masters, C.L., Bush, A.I., Cherny, R.A., Finkelstein, D.I. (2009). Clioquinol Protects Against Cell Death in Parkinson’s Disease Models In Vivo and In Vitro. In: Groenewegen, H., Voorn, P., Berendse, H., Mulder, A., Cools, A. (eds) The Basal Ganglia IX. Advances in Behavioral Biology, vol 58. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0340-2_33
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