AccScience Publishing / AN / Volume 3 / Issue 4 / DOI: 10.36922/an.4291
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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 2024, 3(4), 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/ )
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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.
References
  1. Donmez G, Guarente L. Aging and disease: Connections to sirtuins. Aging Cell. 2010;9(2):285-290. doi: 10.1111/j.1474-9726.2010.00548.x

 

  1. Anekonda TS, Reddy PH. Neuronal protection by sirtuins in Alzheimer’s disease. J Neurochem. 2006;96(2):305-313. doi: 10.1111/j.1471-4159.2005.03492.x

 

  1. Donmez G, Outeiro TF. SIRT1 and SIRT2: Emerging targets in neurodegeneration. EMBO Mol Med. 2013;5(3):344-352. doi: 10.1002/emmm.201302451

 

  1. Wood JG, Schwer B, Wickremesinghe PC, et al. Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2018;115(7):1564-1569. doi: 10.1073/pnas.1720673115

 

  1. Rahman M, Nirala NK, Singh A, et al. Drosophila Sirt2/ mammalian SIRT3 deacetylates ATP synthase β and regulates complex V activity. J Cell Biol. 2014;206(2):289-305. doi: 10.1083/jcb.201404118

 

  1. Cheng X, Song C, Du Y, Gaur U, Yang M. Pharmacological treatment of Alzheimer’s disease: Insights from Drosophila melanogaster. Int J Mol Sci. 2020;21(13):4621. doi: 10.3390/ijms21134621

 

  1. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004;101(45):15998-16003. doi: 10.1073/pnas.0404184101

 

  1. Braidy N, Poljak A, Grant R, et al. Differential expression of sirtuins in the aging rat brain. Front Cell Neurosci. 2015;9:167. doi: 10.3389/fncel.2015.00167

 

  1. Pallàs M, Verdaguer E, Tajes M, Gutierrez-Cuesta J, Camins A. Modulation of sirtuins: New targets for antiageing. Recent Pat CNS Drug Discov. 2008;3(1):61-69. doi: 10.2174/157488908783421492

 

  1. Schwer B, Verdin E. Conserved metabolic regulatory functions of sirtuins. Cell Metab. 2008;7(2):104-112. doi: 10.1016/j.cmet.2007.11.006

 

  1. Smith BC, Denu JM. Sirtuins caught in the act. Structure. 2006;14(8):1207-1208. doi: 10.1016/j.str.2006.07.004

 

  1. Omata Y, Lim YM, Akao Y, Tsuda L. Age-induced reduction of autophagy-related gene expression is associated with onset of Alzheimer’s disease. Am J Neurodegener Dis. 2014;3(3):134-142.

 

  1. Xiang L, Nakamura Y, Lim YM, et al. Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor. Aging (Albany NY). 2011;3(11):1098-1109. doi: 10.18632/aging.100396

 

  1. Banerjee KK, Ayyub C, Ali SZ, Mandot V, Prasad NG, Kolthur-Seetharam U. dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep. 2012;2(6):1485-1491. doi: 10.1016/j.celrep.2012.11.013

 

  1. Griswold AJ, Chang KT, Runko AP, Knight MA, Min KT. Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. Proc Natl Acad Sci U S A. 2008;105(25):8673-8678. doi: 10.1073/pnas.0803837105

 

  1. Li H, Wang R. Blocking SIRT1 inhibits cell proliferation and promotes aging through the PI3K/AKT pathway. Life Sci. 2017;190:84-90. doi: 10.1016/j.lfs.2017.09.037

 

  1. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J Neurol Neurosurg Psychiatry. 1999;66(2):137-147. doi: 10.1136/jnnp.66.2.137

 

  1. Guo J, Cheng J, North BJ, Wei W. Functional analyses of major cancer-related signaling pathways in Alzheimer’s disease etiology. Biochim Biophys Acta Rev Cancer. 2017;1868(2):341-358. doi: 10.1016/j.bbcan.2017.07.001

 

  1. Outeiro TF, Kontopoulos E, Altmann SM, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. Science. 2007;317(5837):516-519. doi: 10.1126/science.1143780

 

  1. Biella G, Fusco F, Nardo E, et al. Sirtuin 2 inhibition improves cognitive performance and acts on amyloid-β protein precursor processing in two Alzheimer’s disease mouse models. J Alzheimers Dis. 2016;53(3):1193-1207. doi: 10.3233/JAD-151135

 

  1. O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34:185-204. doi: 10.1146/annurev-neuro-061010-113613

 

  1. Rajasekhar K, Chakrabarti M, Govindaraju T. Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer’s disease. Chem Commun (Camb). 2015;51(70):13434-13450. doi: 10.1039/c5cc05264e

 

  1. Yin J, Han P, Song M, et al. Amyloid-β increases tau by mediating sirtuin 3 in Alzheimer’s disease. Mol Neurobiol. 2018;55(11):8592-8601. doi: 10.1007/s12035-018-0977-0

 

  1. Jeibmann A, Paulus W. Drosophila melanogaster as a model organism of brain diseases. Int J Mol Sci. 2009;10(2):407-440. doi: 10.3390/ijms10020407

 

  1. McGurk L, Berson A, Bonini NM. Drosophila as an in vivo model for human neurodegenerative disease. Genetics. 2015;201(2):377-402. doi: 10.1534/genetics.115.179457

 

  1. Jahn TR, Kohlhoff KJ, Scott M, et al. Detection of early locomotor abnormalities in a Drosophila model of Alzheimer’s disease. J Neurosci Methods. 2011;197(1):186-189. doi: 10.1016/j.jneumeth.2011.01.026

 

  1. Panchal K, Tiwari AK. Miro, a Rho GTPase genetically interacts with Alzheimer’s disease-associated genes (Tau, Aβ42 and Appl) in Drosophila melanogaster. Biol Open. 2020;9(9):bio049569. doi: 10.1242/bio.049569

 

  1. Simon AF, Chou MT, Salazar ED, et al. A simple assay to study social behavior in Drosophila: Measurement of social space within a group. Genes Brain Behav. 2012;11(2):243-252. doi: 10.1111/j.1601-183X.2011.00740.x

 

  1. Cai Q, Gerwin C, Sheng ZH. Syntabulin-mediated anterograde transport of mitochondria along neuronal processes. J Cell Biol. 2005;170(6):959-969. doi: 10.1083/jcb.200506042

 

  1. Pérez MJ, Jara C, Quintanilla RA. Contribution of tau pathology to mitochondrial impairment in neurodegeneration. Front Neurosci. 2018;12:441. doi: 10.3389/fnins.2018.00441

 

  1. Park SH, Lee S, Hong YK, et al. Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer’s disease. Biol Pharm Bull. 2013;36(3):390-398. doi: 10.1248/bpb.b12-00792

 

  1. Freeman M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell. 1996;87(4):651-660. doi: 10.1016/s0092-8674(00)81385-9

 

  1. Arya R, Lakhotia S. A simple nail Polish imprint technique for examination of external morphology of Drosophila eyes. Curr Sci. 2006;90(9):1179-1180.

 

  1. Panchal K, Tiwari AK. Drosophila melanogaster “a potential model organism” for identification of pharmacological properties of plants/plant-derived components. Biomed Pharmacother. 2017;89:1331-1345. doi: 10.1016/j.biopha.2017.03.001

 

  1. Kumar A, Tiwari AK. Molecular chaperone Hsp70 and its constitutively active form Hsc70 play an indispensable role during eye development of Drosophila melanogaster. Mol Neurobiol. 2018;55(5):4345-4361. doi: 10.1007/s12035-017-0650-z

 

  1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457-481. doi: 10.1080/01621459.1958.10501452

 

  1. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50(3):163-170.

 

  1. Hwang S, Jeong H, Hong EH, Joo HM, Cho KS, Nam SY. Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer’s disease models. Biol Open. 2019;8(2):bio036657. doi: 10.1242/bio.036657

 

  1. Robles E. Learning and Memory in a Drosophila melanogaster Model of Alzheimer’s Disease. Honors Theses. 9; 2016. Available from: https://digitalcommons.coastal.edu/honors-theses/9 [Last accessed on 2024 Nov 28].

 

  1. Dissel S. Drosophila as a model to study the relationship between sleep, plasticity, and memory. Front Physiol. 2020;11:533. doi: 10.3389/fphys.2020.00533

 

  1. Chakraborty A, Picardal F. Neutrophilic, nitrate-dependent, Fe(II) oxidation by a Dechloromonas species. World J Microbiol Biotechnol. 2013;29(4):617-623. doi: 10.1007/s11274-012-1217-9

 

  1. Papaliagkas V, Anogianaki A, Anogianakis G, Ilonidis G. The proteins and the mechanisms of apoptosis: A mini-review of the fundamentals. Hippokratia. 2007;11(3):108-113.

 

  1. Liu X, Wei W, Zhu W, et al. Histone deacetylase AtSRT1 links metabolic flux and stress response in arabidopsis. Mol Plant. 2017;10(12):1510-1522. doi: 10.1016/j.molp.2017.10.010

 

  1. Chen P, Nordstrom W, Gish B, Abrams JM. Grim, a novel cell death gene in Drosophila. Genes Dev. 1996;10(14):1773-1782. doi: 10.1101/gad.10.14.1773

 

  1. Goyal L, McCall K, Agapite J, Hartwieg E, Steller H. Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J. 2000;19(4):589-597. doi: 10.1093/emboj/19.4.589

 

  1. Nordstrom W, Chen P, Steller H, Abrams JM. Activation of the reaper gene during ectopic cell killing in Drosophila. Dev Biol. 1996;180(1):213-226. doi: 10.1006/dbio.1996.0296

 

  1. Farkhondeh T, Mehrpour O, Buhrmann C, Pourbagher- Shahri AM, Shakibaei M, Samarghandian S. Organophosphorus compounds and MAPK signaling pathways. Int J Mol Sci. 2020;21(12):4258. doi: 10.3390/ijms21124258

 

  1. La Marca JE, Richardson HE. Two-faced: Roles of JNK signalling during tumourigenesis in the Drosophila model. Front Cell Dev Biol. 2020;8:42. doi: 10.3389/fcell.2020.00042

 

  1. You H, Lei P, Andreadis ST. JNK is a novel regulator of intercellular adhesion. Tissue Barriers. 2013;1(5):e26845. doi: 10.4161/tisb.26845

 

  1. Killick R, Ribe EM, Al-Shawi R, et al. Clusterin regulates β-amyloid toxicity via dickkopf-1-driven induction of the wnt-PCP-JNK pathway. Mol Psychiatry. 2014;19(1):88-98. doi: 10.1038/mp.2012.163

 

  1. Yarza R, Vela S, Solas M, Ramirez MJ. c-Jun N-terminal Kinase (JNK) signaling as a therapeutic target for Alzheime’s disease. Front Pharmacol. 2016;6:321. doi: 10.3389/fphar.2015.00321

 

  1. Zhu X, Castellani RJ, Takeda A, et al. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: The ‘two hit’ hypothesis. Mech Ageing Dev. 2001;123(1):39-46. doi: 10.1016/s0047-6374(01)00342-6

 

  1. Morishima Y, Gotoh Y, Zieg J, et al. Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci. 2001;21(19):7551-7560. doi: 10.1523/JNEUROSCI.21-19-07551.2001

 

  1. Suwanna N, Thangnipon W, Soi-Ampornkul R. Neuroprotective effects of diarylpropionitrile against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons. Neurosci Lett. 2014;578:44-49. doi: 10.1016/j.neulet.2014.06.029

 

  1. Xu K, Chen W, Wang X, et al. Autophagy attenuates the catabolic effect during inflammatory conditions in nucleus pulposus cells, as sustained by NF-κB and JNK inhibition. Int J Mol Med. 2015;36(3):661-668. doi: 10.3892/ijmm.2015.2280

 

  1. Roncarati R, Sestan N, Scheinfeld MH, et al. The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling. Proc Natl Acad Sci U S A. 2002;99(10):7102-7107. doi: 10.1073/pnas.102192599

 

  1. Woo HN, Park JS, Gwon AR, Arumugam TV, Jo DG. Alzheimer’s disease and Notch signaling. Biochem Biophys Res Commun. 2009;390(4):1093-1097. doi: 10.1016/j.bbrc.2009.10.093

 

  1. Wang ZH, Gong K, Liu X, et al. C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer’s disease. [published correction appears in Nat Commun. 2019;10(1):5452. doi: 10.1038/s41467-019-13553-z]. Nat Commun. 2018;9(1):1784. doi: 10.1038/s41467-018-04120-z

 

  1. Panwar A, Khan MI, Kumar R, Kumar R, Rai SK, Kumar A. Emerging Novel therapeutic approaches for the treatment of Alzheimer’s disease. Adv Alzheimers Dis. 2024;13(3):65-94. doi: 10.4236/aad.2024.133006

 

  1. Athar T, Al Balushi K, Khan SA. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol Biol Rep. 2021;48(7):5629-5645. doi: 10.1007/s11033-021-06512-9

 

  1. Jeon Y, Lee JH, Choi B, Won SY, Cho KS. Genetic dissection of Alzheimer’s disease using Drosophila models. Int J Mol Sci. 2020;21(3):884. doi: 10.3390/ijms21030884
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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