LINGO-1 is a transmembrane protein coded
for by the lingo1 gene, which binds receptors known as NgR1 and
p75, thus preventing them from modulating RhoA [5]. RhoA is
thought to be an important protein in the signal transduction pathway that
stimulates oligodendrocyte differentiation and myelination. Therefore,
overexpression of LINGO-1 results in a lack of oligodendrocyte differentiation,
and inhibition of LINGO-1 is thought to increase myelination
[6].
Recently, anti-LINGO-1 antibodies produced in mice were shown to be
able to effectively remyelinate axons in a demyelinated rat spinal cord
[7]. In Figure 2 (below), the left section of the spinal cord
represents a normal myelinated axon stained with Luxol Fast Blue.
The myelinated axons (on the outside) show a rich teal
color. In the central section, representing demyelinated axons
treated with Immunoglobulin-G, the teal is much paler, and several
parts of the spinal cord do not even take up the stain. The right
panel, treated with anti-LINGO-1 antibodies, shows a darker teal and
indicates that the antibodies are far better at restoring myelination
than the Immunoglobin-G.
This recent study
gives hope that a similar gene therapy involving a recombinant human
anti-LINGO-1 antibody would be successful in promoting remyelination of the
human spinal cord.
