Genetic modifiers of tauopathy in Drosophila

Shulman, Joshua M; Feany, Mel B

doi:10.1093/genetics/165.3.1233

Cited by 256Alzheimer's disease research and treatmentsNeurobiology and Insect Physiology ResearchAmyotrophic Lateral Sclerosis Research

Genetic modifiers of tauopathy in Drosophila

Shulman, Joshua M, Feany, Mel B·2003·Genetics

DOI 10.1093/genetics/165.3.1233

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Abstract

In Alzheimer's disease and related disorders, the microtubule-associated protein Tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles. Mutations in the tau gene cause familial frontotemporal dementia. To investigate the molecular mechanisms responsible for Tau-induced neurodegeneration, we conducted a genetic modifier screen in a Drosophila model of tauopathy. Kinases and phosphatases comprised the major class of modifiers recovered, and several candidate Tau kinases were similarly shown to enhance Tau toxicity in vivo. Despite some clinical and pathological similarities among neurodegenerative disorders, a direct comparison of modifiers between different Drosophila disease models revealed that the genetic pathways controlling Tau and polyglutamine toxicity are largely distinct. Our results demonstrate that kinases and phosphatases control Tau-induced neurodegeneration and have important implications for the development of therapies in Alzheimer's disease and related disorders.

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Increased par-1 expression suppressed mutant tau-induced toxicity.
“whereas Shulman and Feany (52) found that increased par-1 expression suppressed mutant tau-induced toxicity”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [52]
Here we report novel modifiers distinct from those identified in two recent reports that also screened for genetic modifiers of tau-induced neurodegeneration in Drosophila.
“Here we report novel modifiers distinct from those identified in two recent reports that also screened for genetic modifiers of tau-induced neurodegeneration in Drosophila (52,98).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [52]

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Authors: Shulman, J. M., & Feany, M. B.
Affiliations: Brigham and Women's Hospital (US)
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
ORCID: Shulman, Joshua M
Venue: Genetics
Publisher: Oxford University Press (OUP)
Published: 2003-11-01
Volume: 165
Issue: 3
Pages: 1233-1242
ISSN: 0016-6731 (ISSN-L)
1943-2631
DOI: 10.1093/genetics/165.3.1233
OpenAlex: W2145631524
Cited by: 256
References: 89
Citations by year: 2026: 2 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 14 · 2012: 17
FWCI: 7.60
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ns041536-05, 5r01ag019790-05)
National Institute on Aging (AG-19790, AG88001)
National Institute of Neurological Disorders and Stroke (NS41536)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords: tauopathy, tau hyperphosphorylation, genetic modifiers, Drosophila model, kinases, phosphatase, neurodegeneration, Alzheimer's disease, frontotemporal dementia, polyglutamine toxicity, neurofibrillary tangles
MeSH terms: Alzheimer Disease, Animals, Disease Models, Animal, Drosophila, Peptides, tau Proteins, Apoptosis, Animals, Genetically Modified

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Genetic modifiers of tauopathy in Drosophila

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