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 α-synuclein (α-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 α-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified α-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 α-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified α-Syn from brain tissue. Moreover, 15Nitrogen-labeled α-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in α-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.

Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research Ahmedabad Opposite Air force Station Palaj Gandhinagar Gujarat 382355 India

Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research Ahmedabad Opposite Air force Station Palaj Gandhinagar Gujarat 382355 India

Department of Physiology Faculty of Medicine Masaryk University Brno 625 00 Czechia

International Clinical Research Center St Anne's University Hospital Brno Brno 602 00 Czech Republic

Citace poskytuje Crossref.org