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@ARTICLE{Richard:163996,
      author       = {Richard, Mélisande and Doubková, Karolína and Nitta,
                      Yohei and Kawai, Hiroki and Sugie, Atsushi and Tavosanis,
                      Gaia},
      title        = {{A} quantitative model of sporadic axonal degeneration in
                      the {D}rosophila visual system.},
      journal      = {The journal of neuroscience},
      volume       = {42},
      number       = {24},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DZNE-2022-00665},
      pages        = {4937-4952},
      year         = {2022},
      note         = {CC BY},
      abstract     = {In human neurodegenerative diseases, neurons undergo axonal
                      degeneration months to years before they die. Here, we
                      developed a system modelling early degenerative events in
                      Drosophila adult photoreceptor cells. Thanks to the
                      stereotypy of their axonal projections, this system delivers
                      quantitative data on sporadic and progressive axonal
                      degeneration of photoreceptor cells. Using this method, we
                      show that exposure of adult female flies to a constant light
                      stimulation for several days overcomes the intrinsic
                      resilience of R7 photoreceptors and leads to progressive
                      axonal degeneration. This was not associated with apoptosis.
                      We furthermore provide evidence that loss of synaptic
                      integrity between R7 and a postsynaptic partner preceded
                      axonal degeneration, thus recapitulating features of human
                      neurodegenerative diseases. Finally, our experiments
                      uncovered a role of postsynaptic partners of R7 to initiate
                      degeneration, suggesting that postsynaptic cells signal back
                      to the photoreceptor to maintain axonal structure. This
                      model can be used to dissect cellular and circuit mechanisms
                      involved in the early events of axonal degeneration,
                      allowing for a better understanding of how neurons cope with
                      stress and lose their resilience capacities.SIGNIFICANCE
                      STATEMENT:Neurons can be active and functional for several
                      years. In the course of ageing and in disease conditions
                      leading to neurodegeneration, subsets of neurons lose their
                      resilience and start dying. What initiates this turning
                      point at the cellular level is not clear. Here, we developed
                      a model allowing to systematically describe this phase. The
                      loss of synapses and axons represents an early and
                      functionally relevant event towards degeneration. Utilizing
                      the ordered distribution of Drosophila photoreceptors axon
                      terminals, we assembled a system to study sporadic
                      initiation of axon loss and delineated a role for
                      non-cell-autonomous activity regulation in the initiation of
                      axon degeneration. This work will help shedding light on key
                      steps in the etiology of non-familial cases of
                      neurodegenerative diseases.},
      keywords     = {Animals / Axons: physiology / Drosophila: physiology /
                      Drosophila Proteins: genetics / Female / Neurodegenerative
                      Diseases / Synapses: physiology},
      cin          = {AG Tavosanis},
      ddc          = {610},
      cid          = {I:(DE-2719)1013018},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9188428},
      pubmed       = {pmid:35534228},
      doi          = {10.1523/JNEUROSCI.2115-21.2022},
      url          = {https://pub.dzne.de/record/163996},
}