AUTHOR=Micucci Matteo , Gianfanti Federico , Donati Zeppa Sabrina , Annibalini Giosuè , Canonico Barbara , Fanelli Fabiana , Saltarelli Roberta , Osman Riham , Montanari Mariele , Lopez Daniele , Nasoni Gemma , Panza Giovanna , Bargagni Erik , Luchetti Francesca , Retini Michele , Mari Michele , Zappia Giovanni , Stocchi Vilberto , Bartolacci Alessia , Burattini Sabrina , Battistelli Michela 

TITLE=Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1525103

DOI=10.3389/fmolb.2025.1525103

ISSN=2296-889X

ABSTRACT=BackgroundMitochondrial 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.MethodsHT22 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.ResultsQ-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.ConclusionThese 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.