Title:Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis
Volume: 24
Issue: 19
Author(s): Elena Fetisova, Boris Chernyak*, Galina Korshunova, Maria Muntyan*Vladimir Skulachev
Affiliation:
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow,Russian Federation
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow,Russian Federation
Keywords:
Multiple sclerosis, oligodendrocytes, demyelination, inflammasome, mitochondria, reactive oxygen
species, mitochondria-targeted antioxidants, neuroprotection.
Abstract: Background: Multiple sclerosis (MS) is one of the most widespread chronic neurological
diseases that manifests itself by progressive demyelination in the central nervous system.
The study of MS pathogenesis begins with the onset of the relapsing–remitting phase of
the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/
remyelination in the white matter. The following progressive phase is accompanied
by severe neurological symptoms when demyelination and neurodegeneration are spread
to both gray and white matter. In this review, we discuss a possible role of mitochondrial reactive
oxygen species (mtROS) in MS pathogenesis, mechanisms of mtROS generation and effects
of some mitochondria-targeted antioxidants as potential components of MS therapy.
Results: In the early phase of MS, mtROS stimulate NLRP3 inflammasomes, which is critical
for the formation of local inflammatory lesions. Later, mtROS contribute to blood-brain barrier
disruption induced by mediators of inflammation, followed by infiltration of leukocytes. ROS
generated by leukocytes and activated microglia promote mitochondrial dysfunction and oligodendrocyte
cell death. In the progressive phase, neurodegeneration also depends on excessive
mtROS generation. Currently, only a few immunomodulatory drugs are approved for
treatment of MS. These drugs mainly reduce the number of relapses but do not stop MS progression.
Certain dietary and synthetic antioxidants have demonstrated encouraging results in
animal models of MS but were ineffective in the completed clinical trials.
Conclusion: Novel mitochondria-targeted antioxidants could be promising components of
combined programs for MS therapy considering that they can be applied at extremely low
doses and concurrently demonstrate anti-inflammatory and neuroprotective activities.
