The protective effect of MitoQ on Aβ42 induced mitochondrial dysfunction in SH-SY5Y neuroblastoma cells, an in vitro model of Alzheimer's Disease

INTRODUCTION: The rising incidence of neurodegenerative diseases, particularly Alzheimer's disease (AD), has paralleled increased human life expectancy, severely affecting patient quality of life and imposing a burden on healthcare systems. Mitochondrial dysfunction has been recognized as a critical factor in AD pathogenesis.This study investigates the protective effects of MitoQ, a mitochondria-targeted antioxidant, on SH-SY5Y cells treated with amyloid-beta (Aβ42), mimicking AD pathology.
METHODS: SH-SY5Y neuroblastoma cells were exposed to Aβ42 to induce AD-like features, followed by MitoQ treatment. Markers of mitochondrial dysfunction were assessed, including reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and protein expression of antioxidant and mitochondrial-related genes (SODs, CAT, BACE2, ATPs, COIs, TRAKs, OPA1).
RESULTS: MitoQ significantly reduced ROS levels and restored MMP. It also upregulated antioxidant genes (SODs, CAT, BACE2) and OPA-1 expression, while downregulating ATPs, COIs, and TRAKs associated with mitochondrial stress.
DISCUSSION AND CONCLUSION: We successfully created an Alzheimer's model utilizing Aβ42 and studied the effect of the mitochondria-targeted antioxidant molecule, MitoQ, on oxidative stress and mitochondrial dysfunction in this work. We discovered substantial changes in gene and protein expression, as well as changes in mitochondrial membrane structure. These findings, together with MitoQ's possible therapeutic benefits, indicate the drug's potential as a treatment for Alzheimer's disease. Animal investigations are needed to corroborate these findings and get more accurate insights, especially in organs immediately impacted, such as the brain.

Keywords: Alzheimer’s Disease, MitoQ, Mitochondrial Dysfunction, Neurodegeneration