# Influence of Nitrative Stress on the Synthesis of Neuromelanin Model Systems

## TL;DR

This study explores how nitrative stress affects the synthesis of neuromelanin models, which are important for understanding Parkinson's disease.

## Contribution

The study reveals how nitration influences melanin synthesis and conjugate formation in neuromelanin models.

## Key findings

- Nitration on the protein component does not affect conjugate synthesis.
- Increasing nitration on the melanic component inhibits melanization.
- 6-nitrodopamine is incorporated into the conjugate in the presence of dopamine.

## Abstract

Neuromelanin is a
dark pigment present in the human brain and involved
in the onset of Parkinson’s disease. Since natural pigment
can only be extracted from the human brain in very small quantities,
synthetic models of neuromelanin have been developed in recent years
for research purposes, consisting of melanin conjugates and proteins
made up of dopamine and β-lactoglobulin. Here, we studied the
influence of nitrative stress on the synthesis of neuromelanin models,
as it is known that reactive nitrogen species are present in vivo under pathophysiological conditions. HPLC-MS/MS
analysis and 1H NMR and UV–vis absorption spectra
show that nitration on the protein component does not affect the conjugate
synthesis, while increasing nitration on the melanic component, by
replacing dopamine with its nitrate derivative, 6-nitrodopamine, gradually
inhibits the melanization. Moreover, although 6-nitrodopamine is not
able to trigger melanization alone, in the presence of dopamine, it
is incorporated into the conjugate. This study represents a step forward
toward the synthesis of models that are increasingly similar to human
neuromelanin, considering the influence of nitrative stress on neuromelanin
pigment properties and biosynthesis.