Abstract: Parkinson’s disease (PD) motor symptoms are induced by the loss of dopaminergic neurons containing neuromelanin in the nigrostriatal system. The exact mechanism that triggers the degeneration of the nigrostriatal neurons is still unknown but there is general consensus in the scientific community that mitochondrial dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, protein degradation dysfunction of both lysosomal and proteasomal systems, endoplasmic reticulum stress, neuroinflammation and oxidative stress are involved in the degeneration of dopaminergic neurons containing neuromelanin. The pigmentation of dopaminergic neurons in the substantia nigra results from dopamine oxidation to neuromelanin. The hydroxyl groups of the dopamine catechol structure oxidize to carbonyl groups generating quinones. Dopamine oxidizes to dopamine ortho-quinone that is completely unstable at physiological pH and cyclizes spontaneously to aminochrome. Aminochrome is the most stable quinone formed during dopamine oxidation to neuromelanin; it can be one- or two-electron reduced by flavoenzymes or form adducts with proteins such as alpha synuclein, parkin, dopamine transporter, and other proteins. Interestingly, aminochrome has been reported to induce mitochondrial dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, protein degradation dysfunction, endoplasmic reticulum stress, neuroinflammation and oxidative stress (Figure 1; for a review, see Segura-Aguilar, 2019). Therefore, we have proposed that aminochrome is the endogenous neurotoxin formed in neurons containing neuromelanin that triggers the degeneration of the nigrostriatal neurons in PD.