Parkinson’s disease (PD) is caused by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). The incidence of PD increases with age and is one of the major causes of disability. PD early diagnosis is still a challenge as it is based on the clinical assessment of the subject discarding other potential causes of parkinsonism, and the patient’s positive response to Levodopa therapy, leading to a misdiagnosis rate of approximately 16%. The substantia nigra (SN), located in the ventral tegmentum of the midbrain, is divided into two main regions: the iron-rich ventral SN pars reticulata (SNr), and the dorsal SNc, where the neuromelanin-containing dopaminergic neurons (NM) are located. NM is believed to have a neuroprotective function against the toxicity of iron-mediated oxidative processes. Specifically, the death of dopaminergic neurons of the SNc causes NM depigmentation, followed by an increase of iron load. Indeed, it has been reported that a relative decrease of SNc NM leads to a relative increase of SNc iron in PD patients, when compared with age-matched healthy controls (HCs).