A new mechanism for dopaminergic neurons protection mediated by astrocytes For a long time, the question about the mechanism involved in the degenerative process of the nigrostriatal system in Parkinson’s disease (PD), resulting in the loss of dopaminergic neurons containing neuromelanin, has remained open. The discovery of genes associated with familial forms of PD, such as α-synuclein (SNCA), parkin, DJ-1, PINK-1, LRRK-2, ATP13A2, PINK-1 and others resulted in important input into the basic research in this field with the aim of understanding the role of these proteins in sporadic PD. In the scientific community, there is a general agreement that the loss of dopaminergic neurons containing neuromelanin in the nigrostriatal system involves mitochondria dysfunction, protein degradation dysfunction, and SNCA aggregation in neurotoxic oligomers, oxidative stress, neuroinflammation and endoplasmic reticulum stress.
Prof. Juan Segura-Aguilar (University of Chile, Chile) proposed that the neurotoxin involved in the degenerative process of the dopaminergic nigrostriatal system must be of endogenous origin, since the progression of the neurodegenerative process in PD is very slow and takes years for the development of motor symptoms, when up to 60–70% of dopaminergic neurons containing neuromelanin are lost. The slow progression of the degenerative process in PD contrasts with the extremely rapid degeneration observed in humans who are injected with drugs containing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), who after only 3 days develop severe motor symptoms. The possibility that o-quinones derived from dopamine oxidation are responsible for the loss of dopaminergic neurons containing neuromelanin in PD is supported by the fact that these neurons require dopamine oxidation to o-quinones to generate neuromelanin. Interestingly, o-quinones generated during dopamine oxidation have been reported to induce mitochondria dysfunction, SNCA aggregation in neurotoxic oligomers, protein degradation dysfunction of both proteasomal and lysosomal systems and oxidative stress.