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Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease

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Abstract

Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of neurodegenerative disorders by switching between deacetylation and acetylation processes. Histone acetylation occurs when acetyl groups are added to lysine residues on the N-terminal part of histone proteins. Deacetylation, on the other hand, results in the removal of acetyl groups. Pharmacological modulation of sirtuin activity has been shown to influence various neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, and amyotrophic lateral sclerosis. In this review, mechanistic perspective of sirtuins has been discussed in anti-inflammatory, antiapoptotic, and neuroprotective effects in various disorders. We have discussed the structure, neurobiology, and physiology of sirtuins in neurodegenerative disease. Recent preclinical and clinical studies and their outcome have also been elucidated. The aim of this review is to fill in the gaps in our understanding of sirtuins’ role in histone acetylation and deacetylation in all neurodegenerative diseases. Here, we emphasized on reviewing all the studies carried out in various labs depicting the role of sirtuin modulators in neuroprotection and highlighted the ideas that can be considered for future perspectives. Taken together, sirtuins may serve as a promising therapeutic target for the treatment of neurodegenerative disorders.

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Abbreviations

NAD+:

nicotinamide adenine dinucleotide

NDD:

neurodegenerative disease

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

HD:

Huntington’s disease

ALS:

amyotrophic lateral sclerosis

NMN:

nicotinamide mononucleotide

NAMPT:

nicotinamide phosphoribosyltransferase

NMNAT:

nicotinamide/nicotinic acid mononucleotide adenylyltransferase

ETC:

electron transport chain

eNOS:

endothelial nitric oxide synthase

VEGF:

vascular endothelial growth factor

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India, for providing the necessary facilities to carry out the research work.

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  1. Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India

    Heena Khan, Palak Tiwari, Amarjot Kaur & Thakur Gurjeet Singh

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  1. Heena Khan
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  2. Palak Tiwari
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  3. Amarjot Kaur
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Conceptualization: Conceived and designed the experiments: Thakur Gurjeet Singh. Analyzed the data: Amarjot Kaur Grewal & Heena Khan. Wrote the manuscript: Heena Khan, Palak Tiwari. Editing of the Manuscript: Amarjot Kaur & Thakur Gurjeet Singh. Critically reviewed the article: Thakur Gurjeet Singh. All authors read and approved the final manuscript.

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Correspondence to Thakur Gurjeet Singh.

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Khan, H., Tiwari, P., Kaur, A. et al. Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease. Mol Neurobiol 58, 3903–3917 (2021). https://doi.org/10.1007/s12035-021-02387-w

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