Parkinson's disease is characterized by neuronal death in the substantia nigra 
and the presence of intracellular inclusions of α-synuclein in the Lewy bodies. 
Several lines of data support a role for iron in Parkinson's disease: iron is 
present in Lewy bodies, iron accumulates in the dopaminergic neurons in the 
substantia nigra, and Parkinson's disease is correlated with polymorphisms of 
several genes implicated in iron metabolism. Furthermore, iron can compromise 
the solubility of α-synuclein through direct interaction and can induce 
neurotoxicity in vitro. Here, we investigate the possible neuroprotective effect 
of the iron chelator deferoxamine in vivo to elucidate whether iron chelation 
can provide meaningful therapy for Parkinson's disease. Hence, we used a 
Parkinson's disease animal model based on unilateral injection of a recombinant 
adeno-associated viral vector encoding α-synuclein in the rat midbrain. Rats 
were treated with a novel deferoxamine delivery approach: 6 mg of the compound 
was administered intranasally three times a week for 3 or 7 weeks. The behavior 
of the animals and histopathological changes in the brain were analyzed. Our 
data show that although intranasal administration of deferoxamine in rats did 
not protect them from dopaminergic cell death, it did decrease the number of the 
pathological α-synuclein formations at the terminal level. In addition, this 
treatment resulted in changes in the immune response and an overall partial 
improvement in motor behavior. Taken together, our data show that in vivo iron 
chelation can modulate α-synuclein-induced pathology in the central nervous 
system. Our data suggest that chronic administration of intranasal deferoxamine 
may be a valid approach to limiting the mishandling of α-synuclein in the 
central nervous system observed in Parkinson's disease and slowing disease 
progression.