Iron-Induced Dopaminergic Cell Death In Vivo as a Model of Parkinson’s Disease

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. The most striking neuropathological characteristic of PD is the relatively specific loss of neuromelanin (NM)-containing dopaminergic neurons of the substantia nigra (SN) pars compacta and the resulting pallor of the midbrain, as well as the development of abnormal a-synuclein-immunopositive inclusion bodies within the boundaries of the pigment. While the trigger for this relatively selective neuronal vulnerability remains unknown, the cascade of degenerative events leading to cell death is beginning to be understood. The major hypotheses believed to contribute to the eventual demise of nigral dopamine-producing cells include altered protein handling, disturbed iron homeostasis, oxidative stress, mitochondrial dysfunction, and neuroinflammation. The objective of this review is to briefly analyze the evidence for an increased iron content in PD SN and NM as a potential source of increased iron. In addition, findings showing that intranigral iron injections induce dopaminergic nerve cell death in the rat that reproduces key features of PD and mimics molecular mechanisms underlying dopaminergic cell death in PD will be discussed.