But why inhibiting excessive mitochondrial fission inhibits the pathology of neurodegenerative diseases, such as ALS? We propose that P110 treatment inhibited the vicious cycle triggered by protein aggregation, elevation of ROS, and reduction of mitochondrial function and ATP production due to excessive/pathological mitochondrial fission (Fig 6). By inhibiting Drp1/Fis1 interaction (without affecting physiological fission), mitochondrial mass and integrity increase, leading to increased ATP levels that enable better cell repair and protein quality control, and lower mitochondrial‐driven ROS production. We found P110‐induced inhibition of many processes related to oxidative stress, including ALS‐increased ER stress (Lautenschlaeger et al, 2012; Manfredi & Kawamata, 2016), activation of JNK‐related stress (Lee et al, 2016); increased ROS levels (Barber et al, 2006) and macromolecule carbonylation [through 4‐HNE adduction (Niebroj‐Dobosz et al, 2004)], inhibition of autophagy and reduced protein quality control [through reduced proteasome degradative activity (Kabashi & Durham, 2006; Dantuma & Bott, 2014), reduced elimination of misfolded proteins (Nedelsky et al, 2008)], and increased apoptosis triggers (Fig 6). Therefore, P110‐induced better functioning mitochondria resulted in healthier neurons and muscle and improved motor functions in the mice. Importantly, P110 showed benefit in our study although the treatment was initiated only when the animals showed clinical symptoms of dragging feet/knuckles. As ALS patients are diagnosed after the symptoms become quite severe (Takei et al, 2017; Woolley & Rush, 2017), we propose that an inhibitor of Drp1‐hyperactivation, such as P110, may be useful in preventing or slowing the progression of ALS in humans.