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.
Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function
Micucci, Matteo;Gianfanti, Federico;Donati Zeppa, Sabrina;Canonico, Barbara;Fanelli, Fabiana;Saltarelli, Roberta;Osman, Riham;Montanari, Mariele;Lopez, Daniele;Nasoni, Gemma;Panza, Giovanna;Bargagni, Erik;Luchetti, Francesca;Retini, Michele;Mari, Michele;Bartolacci, Alessia;Burattini, Sabrina;Battistelli, Michela
2025
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
