Guys, could it be that sigmaR1 activation and subsequent coupling of mitochondria is basically needed for mitochindria to hitch a ride and be transported down the distant axonal tracks of neurons? Pathophysiological failure of this train system leads to breakdown of synaptic transmission, demyelination and axon degeneration. Depending on which neuron type is affected we call it DM, AD, PD, MS, ALS, AMS, Chronic pain...