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Kano M, Takanashi M, Oyama G, et al. Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinsons Dis. 2020;6(1):33doi: 10.1038/s41531-020-00137-8.
Kano, M., Takanashi, M., Oyama, G., Yoritaka, A., Hatano, T., Shiba-Fukushima, K., Nagai, M., Nishiyama, K., Hasegawa, K., Inoshita, T., Ishikawa, K. I., Akamatsu, W., Imai, Y., Bolognin, S., Schwamborn, J. C., & Hattori, N. (2020). Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinson's disease, 6(1), 33. https://doi.org/10.1038/s41531-020-00137-8
Kano, Masayoshi, et al. "Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations." NPJ Parkinson's disease vol. 6,1 (2020): 33. doi: https://doi.org/10.1038/s41531-020-00137-8
Kano M, Takanashi M, Oyama G, Yoritaka A, Hatano T, Shiba-Fukushima K, Nagai M, Nishiyama K, Hasegawa K, Inoshita T, Ishikawa KI, Akamatsu W, Imai Y, Bolognin S, Schwamborn JC, Hattori N. Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinsons Dis. 2020 Nov 13;6(1):33. doi: 10.1038/s41531-020-00137-8. PMID: 33298969; PMCID: PMC7666226.
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NPJ Parkinsons Dis. 2020 Nov 13;6(1):33. doi: 10.1038/s41531-020-00137-8.

Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations.

NPJ Parkinson's disease

Masayoshi Kano, Masashi Takanashi, Genko Oyama, Asako Yoritaka, Taku Hatano, Kahori Shiba-Fukushima, Makiko Nagai, Kazutoshi Nishiyama, Kazuko Hasegawa, Tsuyoshi Inoshita, Kei-Ichi Ishikawa, Wado Akamatsu, Yuzuru Imai, Silvia Bolognin, Jens Christian Schwamborn, Nobutaka Hattori

Affiliations

  1. Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
  2. Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan. [email protected].
  3. Department of Neurology, Juntendo Koshigaya Hospital, 560 Fukuroyama, Koshigaya, Saitama, 343-0032, Japan.
  4. Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
  5. Department of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0737, Japan.
  6. Department of Neurology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa, 252-0392, Japan.
  7. Department of Neurodegenerative and Demented Disorders, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
  8. Center for Genomic and Regeneration Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
  9. Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
  10. Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 Avenue du Swing, L-4367, Belvaux, Luxembourg.
  11. Braingineering Technologies SARL, 9 Avenue des Hauts-Forneaux, L-4362, Esch-sur-Alzette, Luxembourg.
  12. Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan. [email protected].

PMID: 33298969 PMCID: PMC7666226 DOI: 10.1038/s41531-020-00137-8

Abstract

Parkin (encoded by PRKN) is a ubiquitin ligase that plays an important role in cellular mitochondrial quality control. Mutations in PRKN cause selective dopaminergic cell loss in the substantia nigra and are presumed to induce a decrease in mitochondrial function caused by the defective clearance of mitochondria. Several studies have demonstrated that parkin dysfunction causes mitochondrial injury and astrocytic dysfunction. Using immunohistochemical methods, we analyzed astrocytic changes in human brains from individuals with PRKN mutations. Few glial fibrillary acidic protein- and vimentin-positive astrocytes were observed in the substantia nigra in PRKN-mutated subjects compared with subjects with idiopathic Parkinson's disease. We also differentiated patient-specific induced pluripotent stem cells into midbrain organoids and confirmed decreased numbers of glial fibrillary acidic protein-positive astrocytes in PRKN-mutated organoids compared with age- and sex-matched controls. Our study reveals PRKN-mutation-induced astrocytic alteration and suggests the possibility of an astrocyte-related non-autonomous cell death mechanism for dopaminergic neurons in brains of PRKN-mutated patients.

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