Glial draper rescues Aβ toxicity in a Drosophila model of Alzheimer’s disease

Arpita Ray, Sean Speese, Mary Logan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Pathological hallmarks of Alzheimer’s disease (AD) include amyloid-β (Aβ) plaques, neurofibrillary tangles, and reactive gliosis. Glial cells offer protection against AD by engulfing extracellular Aβ peptides, but the repertoire of molecules required for glial recognition and destruction of Aβ are still unclear. Here, we show that the highly conserved glial engulfment receptor Draper/MEGF10 provides neuroprotection in an AD model of Drosophila (both sexes). Neuronal expression of human Aβ42arc in adult flies results in robust Aβ accumulation, neurodegeneration, locomotor dysfunction, and reduced lifespan. Notably, all of these phenotypes are more severe in draper mutant animals, whereas enhanced expression of glial Draper reverses Aβ accumulation, as well as behavioral phenotypes. We also show that the signal transducer and activator of transcription (Stat92E), c-Jun N-terminal kinase (JNK)/AP-1 signaling, and expression of matrix metalloproteinase-1 (Mmp1) are activated downstream of Draper in glia in response to Aβ42arc exposure. Furthermore, Aβ42-induced upregulation of the phagolysosomal markers Atg8 and p62 was notably reduced in draper mutant flies. Based on our findings, we propose that glia clear neurotoxic Aβ peptides in the AD model Drosophila brain through a Draper/STAT92E/JNK cascade that may be coupled to protein degradation pathways such as autophagy or more traditional phagolysosomal destruction methods.

Original languageEnglish (US)
Pages (from-to)11881-11893
Number of pages13
JournalJournal of Neuroscience
Volume37
Issue number49
DOIs
StatePublished - Dec 6 2017

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Neuroglia
Drosophila
Alzheimer Disease
Diptera
Mitogen-Activated Protein Kinase 8
Phenotype
Peptides
Matrix Metalloproteinase 1
Neurofibrillary Tangles
Gliosis
Cytoprotection
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Autophagy
Amyloid Plaques
Transducers
Proteolysis
Up-Regulation
Brain

Keywords

  • Amyloid
  • Autophagy
  • Draper
  • Drosophila
  • Glia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glial draper rescues Aβ toxicity in a Drosophila model of Alzheimer’s disease. / Ray, Arpita; Speese, Sean; Logan, Mary.

In: Journal of Neuroscience, Vol. 37, No. 49, 06.12.2017, p. 11881-11893.

Research output: Contribution to journalArticle

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