AccScience Publishing / AN / Online First / DOI: 10.36922/an.4291
ORIGINAL RESEARCH ARTICLE

Drosophila Sirtuin 1 plays a neuroprotective role in altering Alzheimer’s disease-related pathologies in flies

Vidhi Bhatt1 Anand Krishna Tiwari1*
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1 Genetics and Developmental Biology Laboratory Department of Biotechnology and Bioengineering, Institute of Advanced Research, Koba, Gandhinagar, Gujarat, India
Advanced Neurology, 4291 https://doi.org/10.36922/an.4291
Submitted: 20 July 2024 | Accepted: 29 October 2024 | Published: 29 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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 with sirtuin overexpression, which modulates c-Jun N-terminal kinase and Notch signaling pathways in flies. These findings show that Sirtuin1 plays a neuroprotective role in AD.

Graphical abstract
Keywords
Sirtuin 1
Alzheimer’s diseases
Drosophila melanogaster
Alzheimer’s disease-related pathologies
Amyloid protein
Histone deacetylase enzymes
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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