Axonal Protective Effects of the Myelin-Associated Glycoprotein

Abstract

Progressive axonal degeneration follows demyelination in many neurological diseases, including multiple sclerosis and inherited demyelinating neuropathies, such as Charcot-Marie-Tooth disease. One glial molecule, the myelin-associated glycoprotein (MAG), located in the adaxonal plasmalemma of myelin-producing cells, is known to signal to the axon and to modulate axonal caliber through phosphorylation of axonal neurofilament proteins. This report establishes for the first time that MAG also promotes resistance to axonal injury and prevents axonal degeneration both in cell culture and in vivo. This effect on axonal stability depends on the RGD domain around arginine 118 in the extracellular portion of MAG, but it is independent of Nogo signaling in the axon. Exploiting this pathway may lead to therapeutic strategies for neurological diseases characterized by axonal loss.

Neuropathy with Predominant Small Fiber Involvement Associated with Abnormal Anti-MAG Titer

“…A possible mechanism of nerve damage in our case can be the presence of immunoglobulin deposition in spinal ganglia; this pattern has been already described in amyloidotic neuropathy in which clinical picture resembles that of our patient (10). On the other hand we cannot exclude an autoimmune attack by anti-MAG autoantibodies on myelinated dermal fibers, which results in damage of their epidermal terminals, or direct damage to epidermal unmyelinated axons deprived of MAG-related protective effects by the antibodies themselves (4,9,11). Further studies are necessary to clarify the complex pathogenesis of this neuropathy.…”

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

“…PROG could protect axons by reducing inflammation, oxidative stress, reactive gliosis, edema, and excitotoxicity, but also preserving the integrity of the myelin sheath. [71][72][73] Otherwise, PROG could have promoted axonal regeneration of supraspinal or propiospinal neurons.…”

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

“…Moreover, the acetylation of tubulin (likely through cytoplasmic acetyltransferases) regulates anterograde and retrograde axonal transport through signaling the anchoring of molecular motors, such as Kinesin-1 to microtubules [93]. As a decrease of acetylated-tubulin has been observed in postmortem brain samples [94], one could predict that a disruption of intracellular trafficking could occur in HD patients, as observed in HD mice neuronal culture and leading to the alteration to the alteration of vesicular BDNF transport [95].…”