Oral resveratrol reduces neuronal damage in a model of multiple sclerosis.
BACKGROUND
Neuronal loss in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), correlates with permanent neurological dysfunction. Current MS therapies have limited the ability to prevent neuronal damage.


METHODS
We examined whether oral therapy with SRT501, a pharmaceutical grade formulation of resveratrol, reduces neuronal loss during relapsing-remitting EAE. Resveratrol activates SIRT1, an NAD+-dependent deacetylase that promotes mitochondrial function.


RESULTS
Oral SRT501 prevented neuronal loss during optic neuritis, an inflammatory optic nerve lesion in MS and EAE. SRT501 also suppressed neurological dysfunction during EAE remission, and spinal cords from SRT501-treated mice had significantly higher axonal density than vehicle-treated mice. Similar neuroprotection was mediated by SRT1720, another SIRT1-activating compound; and sirtinol, an SIRT1 inhibitor, attenuated SRT501 neuroprotective effects. SIRT1 activators did not prevent inflammation.


CONCLUSIONS
These studies demonstrate that SRT501 attenuates neuronal damage and neurological dysfunction in EAE by a mechanism involving SIRT1 activation. SIRT1 activators are a potential oral therapy in MS.
FM Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. kenneth.shindler@uphs.upenn.edu
Kenneth S
KS
Shindler
Elvira
E
Ventura
Mahasweta
M
Dutt
Peter
P
Elliott
Denise C
DC
Fitzgerald
Abdolmohamad
A
Rostami
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D009410:Nerve Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013267:Stilbenes; D000077185:Resveratrol