Aminochrome, a Key Molecule in the Loss of Dopaminergic Neurons Containing Neuromelanin in Idiopathic Parkinson's Disease

One of the biggest problems for researchers working in the field of idiopathic Parkinson's disease and patients is the lack of success in clinical trials attempting to develop new drugs that can slow or halt the progression of the disease. Enormous human and financial resources have been spent on preclinical research that has not led to the discovery of new drugs; however, a serious discussion about the causes of these failures is lacking. In our opinion, the problem lies in the fact that the preclinical studies on which the failed clinical trials were used an exogenous neurotoxin that induce a rapid and expansive degenerative process, which contrasts with the extremely slow degenerative process of idiopathic Parkinson's disease, which takes years. We have proposed that the neurodegenerative process of the nigrostriatal system, which culminates in the loss of dopaminergic neurons containing neuromelanin, is governed by a single-neuron neurodegeneration model. This degenerative process is triggered by the formation of aminochrome within neurons that synthesize neuromelanin, inducing a neurotoxic process without expansive effects on other neurons. This implies that the neurotoxic effects of aminochrome are restricted to a single neuron and that the loss of a single neuron accumulates over time until motor symptoms appear.