4.8 Article

Using multi-organ culture systems to study Parkinson's disease

Journal

MOLECULAR PSYCHIATRY
Volume 26, Issue 3, Pages 725-735

Publisher

SPRINGERNATURE
DOI: 10.1038/s41380-020-00936-8

Keywords

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Funding

  1. Jeanne and Joseph Nissim Center for Life Sciences Research at the Weizmann Institute of Science
  2. Helen and Martin Kimmel Institute for Stem Cell Research
  3. Nella and Leon Benoziyo Center for Neurological Diseases
  4. David and Fela Shapell Family Center for Genetic Disorders Research
  5. Brenden-Mann Women's Innovation Impact Fund
  6. Richard F. Goodman Yale/Weizmann Exchange Program
  7. Irving B. Harris Fund for New Directions in Brain Research
  8. The Irving Bieber, M.D. and Toby Bieber, M.D. Memorial Research Fund
  9. The Leff Family
  10. Dears Foundation
  11. Israel Science Foundation [347/15]
  12. Legacy Heritage Biomedical Program of the Israel Science Foundation [2041/16]
  13. Israel Science Foundation (ISF)-National Natural Science Foundation of China (NSFC) [2449/16]
  14. Canadian Institutes of Health Research (CIHR) [2397/18]
  15. International Development Research Centre (IDRC)
  16. Israel Science Foundation (ISF)
  17. Azrieli Foundation
  18. Ministry of Science & Technology, Israel
  19. The Ministry of Science and Technology of the People's Republic of China
  20. German-Israeli Foundation (GIF) [I-1476-203.13/2018]
  21. United States-Israel Binational Science Foundation (BSF) [2017006]

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Parkinson's disease pathology may manifest earlier in the gastrointestinal track, human induced pluripotent stem cells and organoids aid in disease research, future models should aim to be more complex.
In recent years, it has been revealed that Parkinson's disease pathology may begin to manifest in the gastrointestinal track at a much earlier time point than in the brain. This paradigm shift has been suggested following evidence in humans that has been reproduced in animal models. Since rodent models cannot recapitulate many of the human disease features, human induced pluripotent stem cells derived from Parkinson's patients have been used to generate brain organoids, greatly contributing to our understanding of the disease pathophysiology. To understand the multifaced aspects of Parkinson's disease, it may be desirable to expand the complexity of these models, to include different brain regions, vasculature, immune cells as well as additional diverse organ-specific organoids such as gut and intestine. Furthermore, the contribution of gut microbiota to disease progression cannot be underestimated. Recent biotechnological advances propose that such combinations may be feasible. Here we discuss how this need can be met and propose that additional brain diseases can benefit from this approach.

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