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

Author(s): Nidhi Sharma, Ambika Shandilya, Nitish Kumar, Sidharth Mehan*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 21 , Issue 10 , 2021


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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.

Keywords: SIRT-1, immune dysregulation, multiple sclerosis, neurodegeneration, immune modulators, inflammation.

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Article Details

VOLUME: 21
ISSUE: 10
Year: 2021
Published on: 08 March, 2021
Page: [1845 - 1868]
Pages: 24
DOI: 10.2174/1871530321666210309112234
Price: $95

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