Apomorphine protects against MPTP-induced neurotoxicity in mice

Redox imbalance in Parkinson's disease

“…However, several pieces of biochemical and genetic data also suggest that iron accumulation and subsequent oxidative stress may be a primary event in the degenerative process [50]. A number of iron chelators have been shown to attenuate MPTP toxicity suggesting that iron either mediates or accentuates subsequent neuropathological events associated with its administration [51,52]. Recent studies from our own laboratory, demonstrated that transgenic expression of ferritin or administration of the bioavailable metal chelator clioquinol (CQ) in dopaminergic midbrain neurons protected them from MPTP-mediated neurodegeneration and resulted in an attenuation of motor deficits [53].…”

“…Recent studies from our own laboratory, demonstrated that transgenic expression of ferritin or administration of the bioavailable metal chelator clioquinol (CQ) in dopaminergic midbrain neurons protected them from MPTP-mediated neurodegeneration and resulted in an attenuation of motor deficits [53]. Moreover, studies on iron infusion via unilateral injection or feeding of high iron diet to month old weanling mice demonstrated a significant increase in striatal iron associated with decreases in total glutathione (GSH + GSSG) and increases in hydroxyl radical levels in both the striatum and brainstem suggesting that increases in midbrain iron may be upstream of neurodegeneration associated with PD [54,55]. Recent reports from our laboratory also demonstrated that neonatal iron exposure results in Parkinson-like neurodegeneration with age suggesting that iron accumulation is an early event in dopaminergic cell loss [56].…”

Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases

“…One possible mechanism underlying the effectiveness of green tea and EGCG against MPTP neurotoxicity may involve its catechol-like structure, since it is known that catechol-containing compounds are potent radical anti-oxidants and chelators of ferric ion [44]. In agreement, the iron chelators, radical scavengers, and catechol derivative compounds Rapomorphine (R-APO), dopamine (DA) receptor agonist, and its S-isomer induced neuroprotection in animal models of PD [45,46]. The catechol structural resemblance may account for a recently reported inhibitory effect of green tea polyphenols on [ 3 H] DA uptake by presynaptic transporters.…”

Apomorphine: An underutilized therapy for Parkinson's disease

“…Finally, new experimental findings suggest that apomorphine might be neuroprotective. 11 This review summarizes recent studies with apomorphine in fluctuating PD with or without levodopainduced dyskinesias, the results of which clearly should encourage more widespread use of this potent antiparkinsonian agent. …”