Our previous preclinical, translational and pilot clinical studies demonstrated that novel iron chelation therapy with the prototypic drug deferiprone (DFP) (i) induces neuroprotection in cell models of PD via a powerful antioxidant effect, (ii) reduces regional siderosis of the brain, (iii) reduces motor handicap via inhibition of catechol-o-methyl transferase, and (iv) slows the progression of motor handicap in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
mouse model and in early PD patients.
Initial evidence came from findings that subjects exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) developed PD-like symptoms .
7) Exposure to the insecticide rotenone, (8) the herbicide paraquat (9) and the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) (10) have been shown experimentally to cause mitochondrial dysfunction and subsequent parkinsonism in laboratory animals.
The Parkinson's disease mice model was induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Hydrochloride (MPTP-HC1, 30mg/kg daily for 5 days).
Timecourse of the expression of inflammatory cytokines and matrix metalloproteinases in the striatum and mesencephalon of mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
, a dopaminergic neurotoxin.
The neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
are substrates for the organic cation transporter in renal brush border membrane vesicles.
Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
, by mitochondria.
Among the 30 cases available for review, there are three with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-induced parkinsonism[59,60] and one with possible multiple system atrophy (MSA).
Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
In the study, when administered to rodents that were exposed to neurotoxin kainic acid or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP), clavulanic acid protected neurons in the hippocampus and dopaminergic neurons in the substantia nigra, regions of the brain that are critical in Alzheimer's and Parkinson's disease, respectively.
Increased levels of iron deposits in the SN are observed in postmortem studies , as well as in 6-hydroxydopamine (6-OHDA)  and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)  induced PD animal models.