Title:Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions
Volume: 21
Issue: 10
Author(s): Nidhi Sharma, Ambika Shandilya, Nitish Kumar and Sidharth Mehan*
Affiliation:
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab,India
Keywords:
SIRT-1, immune dysregulation, multiple sclerosis, neurodegeneration, immune modulators, inflammation.
Abstract: Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key
causes for autoimmune disorders like multiple sclerosis (MS) and various other immune dysregulated
neurodegenerative complications responsible for CNS-mediated immune responses. Sirtuin
(SIRT-1) is a nicotinamide adenosine dinucleotide (NAD)-dependent transcriptional protein that
deacetylases and removes acetyl groups from its transcription factors like P53, FOXO, NF-Κb,
PGC-1α. SIRT-1 mediates a wide range of physiological functions, including gene transcription,
metabolism, neuronal apoptosis, and glucose production. SIRT-1 dysregulation targets transcription
factors, and other molecular alterations such as gene expression modification influence neuronal
plasticity, inhibit Th17 cells, and interleukin-1β can aggravate brain diseases. Preclinical and
clinical findings show that the upregulation of SIRT-1 reduces autoimmunity, neurodegeneration,
and neuroexcitation. Even though drugs are being developed for symptomatic therapies in clinical
trials, there are particular pharmacological implications for improving post-operative conditions in
neurodegenerative patients where intensive care is required. Understanding the SIRT-1 signaling
and identifying immune-mediated neuron deterioration can detect major therapeutic interventions
that could prevent neuro complications. Thus, in the current review, we have addressed the manifestations
of disease by the downregulation of SIRT-1 that could potentially cause MS and other neurodegenerative
disorders and provided data on existing available and effective drug therapies and
disease management strategies.
