Multiple (MS) sclerosis is a chronic inflammatory
demyelinating disease of the central nervous system with the
pathological hallmarks of inflammation, demyelination, axon loss
and gliosis. In the initial relapsing-remitting phase of the
disease, the inflammatory-demyelinating component seems to
predominate, whereas the progressive disease appears to be
characterized by a neurodegenerative component leading to
extensive neuroaxonal damage in the MS brain. Axon loss most
likely determines the persistent neurological deficit in
progressive MS. Recent studies pointed out that axon damage
occurs early in the disease and during lesion development. Two
different phases of axon degeneration were characterized, the
first occurring during active myelin breakdown and the second in
chronic demyelinated plaques in which the naked axon seems more
susceptible to further damage. The exact mechanisms and effector
molecules of axonal degeneration, however, are not yet defined,
and an axon-protective therapy has not yet been
established.