Parkinson’s disease (PD) is a neurodegenerative disorder characterized by cardinal motor features, such as bradykinesia, rigidity, postural instability and resting tremor, and non-motor features, ranging from depression to hyposmia. PD is the most common chronic neurodegenerative disease affecting motor behaviour, and its prevalence increases with age, from 2% in over 65 years old to 5% in over 85 years old. PD is characterized by the progressive loss of dopaminergic (DA-ergic) pigmented neurons of the substantia nigra (SN) pars compacta, a small structure lying deep in the core of the human midbrain. Among these neuronal cells, DA is synthesized from the L-3, 4-dihydroxyphenylalanine (L-dopa) deriving from the hydroxylation of tyrosine. This pathway, the only one available in the SN for DA production, leads to DA synthesis in its first stage, eventually producing other catecholamines, such as noradrenaline and adrenaline, by the action of aromatic L-amino acid decarboxylase (AADC; dopa decarboxylase, DDC). From the first depiction, dating back to Parkinson’s original “paralisis agitans”, it took more than a century to unveil the distribution of cathecolamines among the central nervous system (CNS), and almost 40 years to shed light on the dopamine (DA) deficiency peculiar of PD. From such pioneering reports the levodopa (LD) era starts.
