Publication details
Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress
| Authors | |
|---|---|
| Year of publication | 2025 |
| Type | Article in Periodical |
| Magazine / Source | CHEMICAL RESEARCH IN TOXICOLOGY |
| MU Faculty or unit | |
| Citation | |
| web | https://pubs.acs.org/doi/10.1021/acs.chemrestox.4c00348 |
| Doi | https://doi.org/10.1021/acs.chemrestox.4c00348 |
| Keywords | malondialdehyde; alpha-synuclein aggregation; oxidative stress; Parkinson’s disease; protein aggregation |
| Description | Malondialdehyde (MDA), a major reactive byproduct of lipid peroxidation, has been implicated in numerous pathological conditions as a result of altering the structure and function of crucial proteins. One such protein is alpha-synuclein (alpha-Syn), which plays a vital role in the pathogenesis of Parkinson's disease (PD). This study investigates the hypothesis that MDA causes structural alterations in alpha-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified alpha-Syn were injected to the brain of mice. Behavioral assessments were performed to evaluate motor function changes, while immunohistochemistry was employed to examine the extent of alpha-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified alpha-Syn from brain tissue. Moreover, 15Nitrogen-labeled alpha-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in alpha-Syn alter its structural properties and also significantly enhance its aggregation propensity, potentially contributing to the neurodegenerative processes observed in PD. The developed model displayed a nonreversible decline in motor function, neurodegeneration, and aggregation of proteins in the brain mimicking the PD conditions. This research provides valuable insights into the molecular mechanisms of PD, emphasizing the role of MDA-modified proteins in the etiology of PD. |