Lessons Learned from Transgenic Mouse Models for the Therapeutic Use of Drp1 Inhibitors

Licci Maria and Oettinghaus Björn

Pharmacological inhibition of dynamin-related protein 1 (Drp1) the main mammalian promoter of mitochondrial fission - has emerged as a promising therapeutic target for the treatment of neuronal injuries. Genetic studies, however, have revealed that inhibiting Drp1 during development leads to defects especially in neuronal differentiation. Bypassing this neurodevelopmental impairment, a number of recent studies have genetically ablated Drp1 in different adult neuronal subpopulations. This has led to new insights into the importance of mitochondrial fission in differentiated neurons and has highlighted potentially severe side effects of this new therapeutic strategy.