SIRT1 and NADÂ + precursors: Therapeutic targets in multiple sclerosis a review

- Neurodeneration is linked to disability and progression in MS
- Neurodegeneration may be due to an insufficient energy stores in neurons secondary to inflammation in MS
- SIRT1 is a transcriptional regulator that is modulated by the levels of NAD which reflect the energy state of neurons
- SIRT1 is increased in neurons in MS and EAE
- SIRT1 overexpression is neuroprotective in EAE
- SIRT1 agonists are neuroprotective in EAE
- These observations provide a rationale for therapies targeting SIRT1

Neurodegeneration is an important determinant of disability in multiple sclerosis (MS) but while currently approved treatments reduce inflammation, they have not been shown to reduce neurodegeneration. SIRT1, a NAD dependent protein deacetylase, has been implicated in the pathogenesis of neurodegeneration in neurological diseases including MS. We have studied the role of SIRT1 in experimental autoimmune encephalomyelitis (EAE) and found evidence for a neuroprotective role. In this review we summarize the most recent findings from the use of SIRT1 activators and SIRT1 overexpression in transgenic mice. These data support provide a rational for the use of SIRT1 activators in MS.