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Cited by 40Alzheimer's disease research and treatmentsNeurobiology and Insect Physiology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Neuroprotective Effects of PARP Inhibitors in Drosophila Models of Alzheimer’s Disease

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Maggiore, Anna, Casale, Assunta Maria, Toscanelli, Walter, Cappucci, Ugo, Rotili, Dante, Grieco, Maddalena, Gagné, Jean-Philippe, Poirier, Guy G. +2 more·2022·Cells
DOI 10.3390/cells11081284PMC PMC9027574
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Abstract

Alzheimer’s disease (AD) is an irreversible age-related neurodegenerative disorder clinically characterized by severe memory impairment, language deficits and cognitive decline. The major neuropathological hallmarks of AD include extracellular deposits of the β-amyloid (Aβ) peptides and cytoplasmic neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. The accumulation of plaques and tangles in the brain triggers a cascade of molecular events that culminate in neuronal damage and cell death. Despite extensive research, our understanding of the molecular basis of AD pathogenesis remains incomplete and a cure for this devastating disease is still not available. A growing body of evidence in different experimental models suggests that poly(ADP-ribose) polymerase-1 (PARP-1) overactivation might be a crucial component of the molecular network of interactions responsible for AD pathogenesis. In this work, we combined genetic, molecular and biochemical approaches to investigate the effects of two different PARP-1 inhibitors (olaparib and MC2050) in Drosophila models of Alzheimer’s disease by exploring their neuroprotective and therapeutic potential in vivo. We found that both pharmacological inhibition and genetic inactivation of PARP-1 significantly extend lifespan and improve the climbing ability of transgenic AD flies. Consistently, PARP-1 inhibitors lead to a significant decrease of Aβ42 aggregates and partially rescue the epigenetic alterations associated with AD in the brain. Interestingly, olaparib and MC2050 also suppress the AD-associated aberrant activation of transposable elements in neuronal tissues of AD flies.

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  • While these studies stand in slight contrast with an Aβ-based Drosophila model in which several retrotransposon transcripts were found to be elevated, it is clear that pathogenic forms of tau can drive the transcriptional elevation of retrotransposons independently of Aβ.

    “While these studies stand in slight contrast with an Aβ-based Drosophila model in which several retrotransposon transcripts were found to be elevated (Maggiore et al. 2022), it is clear that pathogenic forms of tau can drive the transcriptional elevation of retrotransposons independently of Aβ.”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Maggiore et al. 2022

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Cited by

Sorted by citations

Authors
Maggiore, A., Casale, A. M., Toscanelli, W., Cappucci, U., Rotili, D., Grieco, M., Gagné, J.-P., Poirier, G. G., d’Erme, M., & Piacentini, L.
Affiliations
  • Sapienza University of Rome (IT)
  • Université Laval (CA)
Corresponding author
Piacentini, Lucia
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2022-04-09
Volume
11
Issue
8
Pages
1284
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells11081284
PMC
PMC9027574
OpenAlex
W4223503917
Cited by
40
References
13
Citations by year
2026: 10 · 2025: 14 · 2024: 7 · 2023: 6 · 2022: 2 · 2021: 1
FWCI
4.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Iris (Roma Tre University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
Funders
Sapienza Università di Roma
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, PARP-1 inhibitors, olaparib, neuroprotection, Drosophila model, amyloid-beta aggregation, amyloid-beta 42, transposable elements, epigenetic modifications, lifespan extension, climbing behavior, neurofibrillary tangles, tau hyperphosphorylation, neuronal injury
MeSH terms
Poly(ADP-ribose) Polymerase Inhibitors, Alzheimer Disease, Animals, Drosophila, Amyloid beta-Peptides, Neuroprotective Agents

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