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Humanization for neurological disease modeling: A roadmap to increase the potential of Drosophila model systems

Contributeurs/tricesKatanaev, Vladimirorcid
Publié dansAnimal models and experimental medicine, vol. 6, no. 3, p. 230-236
Date de publication2023-06
Date de mise en ligne2023-05-08
Résumé

Neuroscience and neurology research is dominated by experimentation with rodents. Around 75% of neurology disease-associated genes have orthologs in Drosophila melanogaster, the fruit fly amenable to complex neurological and behavioral investigations. However, non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies. One reason for this situation is the predominance of gene overexpression (and gene loss-of-function) methodologies used when establishing a Drosophila model of a given neurological disease, a strategy that does not recapitulate accurately enough the genetic disease conditions. I argue here the need for a systematic humanization approach, whereby the Drosophila orthologs of human disease genes are replaced with the human sequences. This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly. I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application, and consider its importance for subsequent disease modeling and drug discovery in Drosophila. I argue that this paradigm will not only advance our understanding of the molecular etiology of a number of neurological disorders, but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.

eng
Mots-clés
  • Drosophila
  • Disease modeling
  • Humanization
  • Neurological diseases
  • Animals
  • Rats
  • Mice
  • Humans
  • Drosophila / genetics
  • Drosophila melanogaster / genetics
  • Disease Models, Animal
  • Nervous System Diseases / genetics
  • Drug Discovery
Citation (format ISO)
KATANAEV, Vladimir. Humanization for neurological disease modeling: A roadmap to increase the potential of Drosophila model systems. In: Animal models and experimental medicine, 2023, vol. 6, n° 3, p. 230–236. doi: 10.1002/ame2.12322
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Identifiants
ISSN du journal2576-2095
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Création20/06/2023 14:16:58
Première validation21/06/2023 07:14:26
Heure de mise à jour21/06/2023 07:14:26
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