Transferring organelles into native neurons: A disease-modifying therapy for neurodegenerative disorders
Abstract
Currently, there are no disease-modifying therapies to counter the progression of neurodegenerative diseases that are associated with mitochondrial dysfunction in the early stages. In this study, we have used a novel strategy of cell fusion to transfer mitochondria from one cell to another using fusogens (syncytin 1 and syncytin 2). Syncytins are placental proteins encoded by endogenous retroviral envelope genes that promote cellular fusion. In this study, we have proposed that donor cells engineered to stably express syncytin when cocultured with recipient cells will allow fusion and facilitate the transfer of mitochondria into recipient cells. Syncytin-mediated systems revealed about 16.6-18.5% cell fusion efficiencies in N2a and SH-SY5Y cells. The present work is proof that our strategy of engineering syncytin expression systems allows cell fusion in neurons.
Keywords: neurodegeneration, mitochondria, cell fusion, syncytins, fusion efficiency, heterologous system, engineered, progression, cocultured, mitochondrial transfer