Investigation of therapeutic targets in neuromelanin-induced neurodegeneration
Project no. 22303 · Status: Kapanmış · 2021
Summary
<p>Neuromelanin is an iron-rich, brown or black insoluble pigment that accumulates in brain with age. This pigment, which has antioxidant properties and a protective effect against some drugs, accumulates over time and becomes a source of free radicals. In Parkinson's Disease, neuromelanin releases from cells following dopaminergic neuronal death, affects microglia and causes neuroinflammation. Ferroptosis, a cell death type, has been shown in Parkinson's Disease. However, it is not clearly defined. In this project, we aimed to investigate the possible changes in iron metabolism in neuromelanin-induced neuronal damage and to determine therapeutic targets. In our study, synthetic neuromelanin-exposed cells were used. Following the applications, lipid peroxidation products, GSH, intracellular iron level and ferroptosis parameters (GPX4, Acsl4) were measured using spectrophotometric, microscopic and molecular techniques. The effects of neuromelanin on intracellular iron uptake were evaluated through iron metabolism-related proteins such as transferrin receptor-1, ferroportin, ferritin, IREB2 and DMT1. It has been observed that the application of neuromelanin reduces cell viability, similar to the application of rotenone and erastin (a ferroptosis activator), and these effects can be reversed in the presence of a ferroptosis inhibitor. Additionally, notable changes have been observed in lipid peroxidation, decreased GPX4 levels, and altered iron metabolism following the application of neuromelanin (p<0.05). The detailed examination of an experimental model that can be used in neuromelanin research, the elucidation of the role of neuromelanin in ferroptosis and the identification of the potential therapeutic targets will contribute to the scientific literature. </p>