Sirtuin 3 expression in the context of Relapsing Remitting Multiple Sclerosis
Keywords:
Multiple Sclerosis, MS, Sirtuin, Sirt3, RRMS, NeuroinflammationAbstract
Multiple sclerosis (MS) is a debilitating disease that attacks the myelin sheath surrounding neurons in the central nervous system resulting in focal demyelinated lesions. This process is immune-mediated in nature and is thought to arise following inflammatory and metabolic alterations leading to loss of the myelin sheath. Following this, axons in the afflicted areas may recover and remyelinate or undergo axonal loss leading to eventual neurodegeneration. Current knowledge of the mechanisms involved in lesion formation and neuronal outcomes is limited. A relatively recently identified family of proteins, the sirtuins, have been found to be strongly implicated in inflammation and aging throughout the body. While some work has identified alterations in sirtuins 1 and 2 within animal models and MS samples, no such investigations have examined the related sirtuin 3 (Sirt3) protein. In our current study, we examined Sirt3 expression in MS lesions from post-mortem tissue as well as mRNA levels within CD14+ cells isolated from MS patients and controls. We found reduced Sirt3 expression within MS lesions and trends towards reduced Sirt3 mRNA levels in females as well as MS patients. Overall, our work supports the hypothesis that Sirt3 plays a role in MS, however, further studies are needed to identify the CNS distribution of Sirt3 in MS patients, how Sirt3 alterations impact CD14+ cells in MS, and whether Sirt3 may play a role in the sex differences observed in MS.References
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