Abstract
In multiple sclerosis (MS) disability results from neuronal and axonal loss, the hallmark
of neurodegenerative diseases (ND). Neurodegeneration is initiated by microglia activation
and mediated by oxidative stress and excitotoxicity. The same sequence of events has
been consistently observed in MS. However, microglia activation correlates with a
marked cell infiltration in MS but not in ND. In both pathological states, peroxynitrite
is the common initiating factor of oxidative stress and excitotoxicity and is thus
a potential interesting therapeutic target. Oxidative stress leads to multiple lipid
and protein damages via peroxidation and nitration processes. The pathomechanisms
of excitotoxicity are complex involving glutamate overload, ionic channel dysfunction,
calcium overload, mitochondriopathy, proteolytic enzyme production and activation
of apoptotic pathways. The inflammatory component in MS is important for the design
of therapeutic strategies. Inflammation not only causes axonal and neuronal loss but
it also initiates the degenerative cascade in the early stage of MS. Potent anti-inflammatory
agents are now available and it is not unreasonable to think that an early blockade
of inflammatory processes might also block associated degenerative mechanisms and
delay disability progression. The development of neuroprotective drugs is more problematic.
Indeed, given the multiple and parallel mechanisms involved in neurodegeneration,
modulation of a single specific pathway will likely yield a partial benefit if any.
Keywords
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Article info
Publication history
Accepted:
June 27,
2008
Received:
February 19,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
