Axonal degeneration is a prominent pathological feature in multiple sclerosis observed over
a century ago. The gradual loss of axons is thought to underlie irreversible clinical deficits in
this disease. The precise mechanisms of axonopathy are poorly understood, but likely
involve excess accumulation of Ca ions. In healthy fibers, ATP-dependent pumps support
homeostasis of ionic gradients. When energy supply is limited, either due to inadequate
delivery (eg, ischemia, mitochondrial dysfunction) and/or excessive utilization (eg …