Neurology 2026

The loss of neuromelanin-containing dopaminergic neurons may result from the formation of aminochrome during neuromelanin synthesis, specifically when the dopamine catechol group undergoes oxidation. Aminochrome induces neurodegeneration by triggering mitochondrial dysfunction, the formation of neurotoxic alpha-synuclein oligomers, dysfunction of both lysosomal and proteasomal protein degradation systems, neuroinflammation, endoplasmic reticulum stress, and oxidative stress. However, two enzymes prevent the neurotoxic effects of aminochrome: DT-diaphorase, which is expressed in neuromelanin-containing dopaminergic neurons and astrocytes, and glutathione transferase M2-2, which is expressed solely in astrocytes. Interestingly, astrocytes release exosomes loaded with glutathione transferase M2-2; these exosomes penetrate dopaminergic neurons and release the enzyme into the neuronal cytosol, thereby enhancing neuroprotection against aminochrome.

Juan Segura-Aguilar earned his Ph.D. in biochemistry from Stockholm University in 1989. He worked at Stockholm University and Uppsala University in Sweden, and in 1998 began working at the Faculty of Medicine of the University of Chile. He has been a Full Professor since 2001. His research has focused on the molecular mechanisms of Parkinson's disease. He is currently proposing a new model for the development of idiopathic Parkinson's disease, the "Single-neuron degeneration model." He has 145 publications in PubMed and in 2022 was ranked 115,825 out of 9,071,000 scientists.