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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Drosophila Sirtuin 1 plays a neuroprotective

role in altering Alzheimer’s disease-related
pathologies in flies

Vidhi Bhatt and Anand Krishna Tiwari*

Genetics and Developmental Biology Laboratory Department of Biotechnology and Bioengineering,

Institute of Advanced Research, Koba, Gandhinagar, Gujarat, India

Abstract

Sirtuin, a Class III histone deacetylase enzyme dependent on nicotinamide adenine
dinucleotide, plays a pivotal role in aging and age-related diseases. Numerous
studies have highlighted the involvement of sirtuins in Alzheimer’s and other
neurodegenerative diseases; however, their molecular mechanisms and possible
interactions with Alzheimer’s disease (AD)-associated genes remain unclear. In this
study, using a Drosophila melanogaster model of AD, we investigated the potential
genetic interactions between sirtuin and AD-associated genes, including amyloid-
beta 42, Appl, and Tau. Our findings show that the overexpression or downregulation
of Drosophila Sirtuin 1 alters AD-related pathologies such as the rough eye
phenotype, behavioral impairments, and excessive cell death observed in AD model
flies. In addition, the observed rescue of AD pathologies appears to be associated
*Corresponding author: with sirtuin overexpression, which modulates c-Jun N-terminal kinase and Notch
Anand Krishna Tiwari
(anandk.tiwari@iar.ac.in); signaling pathways in flies. These findings show that Sirtuin1 plays a neuroprotective
role in AD.
Citation: Bhatt V and Tiwari AK.
Drosophila Sirtuin 1 plays a
neuroprotective role in altering Keywords: Sirtuin 1; Alzheimer’s diseases; Drosophila melanogaster; Alzheimer’s disease-
Alzheimer’s disease-related
pathologies in flies. Adv Neurol. related pathologies; Amyloid protein; Histone deacetylase enzymes
2024;3(4):4291.
doi: 10.36922/an.4291
Received: July 20, 2024
1. Introduction
Accepted: October 29, 2024
Sirtuins, a conserved group within the Class III histone deacetylase family, are dependent
Published Online: November 29,
2024 on nicotinamide adenine dinucleotide. They remove acetyl groups from lysine residues
on both histone and non-histone proteins through hydrolysis and are generally known
Copyright: © 2024 Author(s).
1-3
This is an Open-Access article as “lysine deacetylases”. In humans, seven (Sirt1 – 7) and five (Sirt1 [dsir2, Sirt2
distributed under the terms of the [dsirt2, Sirt4 [dsirt4, Sirt6 [dsirt6, and Sirt7 [dsirt7) sirtuin genes have been identified
Creative Commons Attribution in humans and Drosophila melanogaster, respectively. Of the five sirtuin genes, Sirt1
4,5
License, permitting distribution,
and reproduction in any medium, (dsir2) is one of the most conserved genes in D. melanogaster, with its overexpression
provided the original work is shown to prolong the lifespan of fruit flies. Research on Drosophila has highlighted
6,7
properly cited. dsir2 as a crucial gene involved in the anti-aging process. 8-11 One study demonstrated
Publisher’s Note: AccScience that dsir2 and dfoxo are required to maintain the expression of the autophagy-related
Publishing remains neutral with gene atg18 during aging. Earlier studies have also indicated that dsir2, foxo, and 4E-BP
12
regard to jurisdictional claims in 13
published maps and institutional play essential roles in regulating the lifespan of Drosophila. SIRT1, a nuclear protein, is
affiliations. instrumental in lifespan extension, cell cycle regulation, and histone deacetylation. 5,14,15

Volume 3 Issue 4 (2024) 1 doi: 10.36922/an.4291