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Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic

Yu-Hsien Lin1,2, Houda Ouns Maaroufi1,2, Lucie Kucerova1

  • 1Biology Centre of the Czech Academy of Sciences, Institute of Entomology, Ceske Budejovice, Czechia.

Frontiers in Cell and Developmental Biology
|March 29, 2021
PubMed

Insights

Adenosine signaling impacts stress responses in Drosophila. Modulating adenosine pathways, including adenosine receptors and transporters, reduced mortality in flies with mutant huntingtin protein.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Adenosine (Ado) is a key signaling molecule in mammalian stress responses.
  • Its role in Drosophila stress signaling remains largely unexplored.
  • Mutant huntingtin protein (mHTT) is associated with various cellular dysfunctions.

Purpose of the Study:

  • To investigate the role of adenosine signaling in Drosophila stress responses.
  • To determine if adenosine signaling modulates mutant huntingtin protein toxicity in Drosophila.
  • To identify downstream targets of adenosine signaling in this context.

Main Methods:

  • Utilized Drosophila models expressing mutant huntingtin protein (mHTT).
  • Genetically manipulated adenosine signaling components, including transporters and receptors.
  • Assessed mortality rates and formation of mHTT aggregates.
  • Identified downstream targets like Mod(mdg4) and Hsp70.

Main Results:

  • Flies with mHTT exhibited reduced extracellular adenosine and suppressed transporter expression.
  • Overexpressing adenosine metabolic enzymes or suppressing adenosine receptors/transporters mitigated mHTT-induced mortality.
  • Adenosine receptor pathway targets, Mod(mdg4) and Hsp70, influenced mHTT aggregate formation.
  • Altered adenosine signaling affected Drosophila responses to paraquat and heat-shock treatments.

Conclusions:

  • Adenosine signaling plays a crucial role in regulating stress responses in Drosophila.
  • Modulating adenosine pathways offers a potential therapeutic strategy for mHTT-related pathologies.
  • This study elucidates novel mechanisms of adenosine-mediated stress protection in Drosophila.
Keywords:
cytotoxicityequilibrative nucleoside transporterheat-shock protein 70modifier of mdg4mutant huntingtinneurodegeneration

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