Article
作者: Zappia, Giovanni ; Lopez, Daniele ; Bargagni, Erik ; Montanari, Mariele ; Luchetti, Francesca ; Mari, Michele ; Burattini, Sabrina ; Bartolacci, Alessia ; Panza, Giovanna ; Micucci, Matteo ; Stocchi, Vilberto ; Retini, Michele ; Donati Zeppa, Sabrina ; Saltarelli, Roberta ; Canonico, Barbara ; Fanelli, Fabiana ; Osman, Riham ; Annibalini, Giosuè ; Battistelli, Michela ; Gianfanti, Federico ; Nasoni, Gemma
Background:Mitochondrial dysfunction and oxidative stress are central mechanisms in the progression of neurodegenerative diseases. This study first evaluated the toxicity of Q-Der (Q10-diacetate), a derivative of Coenzyme Q10, in HT22 hippocampal neurons under normal and oxidative stress conditions.
Methods:HT22 cells were treated with Q-Der at 2.5, 5 and 10 µM with and without rotenone. Mitochondrial superoxide production (Mitosox), gene expression (via qRT-PCR), and protein levels (via Western blot) were measured. Morphological analyses were performed using transmission (TEM) and scanning (SEM) electron microscopes.
Results:Q-Der significantly reduced mitochondrial superoxide levels, particularly at 5 μM, and upregulated key mitochondrial biogenesis genes, including PGC-1α and TFAM. Additionally, it restored the expression of MT-ND1 and MT-COI, which were downregulated by rotenone. Western blot results showed a significant recovery in CV-ATP5A (complex V) expression (p < 0.05), preserving mitochondrial ATP production. Morphological analyses further confirmed Q-Der’s ability to maintain cellular and mitochondrial structure under stress conditions.
Conclusion:These findings suggest that Q-Der is non-toxic under normal conditions and protects against oxidative stress, supporting its potential as a therapeutic agent for neurodegenerative diseases.
