Figure 2.

The single neuron death induced by aminochrome.

(A) Neuromelanin synthesis in healthy older adults needs the formation of the endogenous neurotoxin aminochrome, but the presence of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2 (GSTM2-2) prevents the toxic effects of aminochrome, which explains why dopaminergic neurons containing neuromelanin are intact when they die. (B) In the patient with idiopathic Parkinson’s disease (PD), for some unknown reason, the enzymes DT-diaphorase and M2-2 glutathione transferase cannot prevent the neurotoxic action of aminochrome, which implies that aminochrome induces mitochondrial dysfunction, formation of neurotoxic oligomers of alpha-synuclein (SNCA), neuroinflammation, endoplasmic reticulum stress, dysfunction of both lysosomal and proteasomal protein degradation systems, and oxidative stress, which generates neurotoxicity that ultimately ends with the loss of a single neuron. Created with ChemDraw.