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Shiba-Fukushima K, Inoshita T, Sano O, et al. A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling. iScience. 2020;23(5):101048doi: 10.1016/j.isci.2020.101048.
Shiba-Fukushima, K., Inoshita, T., Sano, O., Iwata, H., Ishikawa, K. I., Okano, H., Akamatsu, W., Imai, Y., & Hattori, N. (2020). A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling. iScience, 23(5), 101048. https://doi.org/10.1016/j.isci.2020.101048
Shiba-Fukushima, Kahori, et al. "A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling." iScience vol. 23,5 (2020): 101048. doi: https://doi.org/10.1016/j.isci.2020.101048
Shiba-Fukushima K, Inoshita T, Sano O, Iwata H, Ishikawa KI, Okano H, Akamatsu W, Imai Y, Hattori N. A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling. iScience. 2020 May 22;23(5):101048. doi: 10.1016/j.isci.2020.101048. Epub 2020 Apr 11. PMID: 32335362; PMCID: PMC7183160.
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iScience. 2020 May 22;23(5):101048. doi: 10.1016/j.isci.2020.101048. Epub 2020 Apr 11.

A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling.

iScience

Kahori Shiba-Fukushima, Tsuyoshi Inoshita, Osamu Sano, Hidehisa Iwata, Kei-Ichi Ishikawa, Hideyuki Okano, Wado Akamatsu, Yuzuru Imai, Nobutaka Hattori

Affiliations

  1. Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
  2. BioMolecular Research Laboratories, Takeda Pharmaceutical Company, Fujisawa, Kanagawa 251-8555, Japan.
  3. Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
  4. Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
  5. Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
  6. Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: [email protected].
  7. Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: [email protected].

PMID: 32335362 PMCID: PMC7183160 DOI: 10.1016/j.isci.2020.101048

Abstract

Early-onset Parkinson's disease-associated PINK1-Parkin signaling maintains mitochondrial health. Therapeutic approaches for enhancing PINK1-Parkin signaling present a potential strategy for treating various diseases caused by mitochondrial dysfunction. We report two chemical enhancers of PINK1-Parkin signaling, identified using a robust cell-based high-throughput screening system. These small molecules, T0466 and T0467, activate Parkin mitochondrial translocation in dopaminergic neurons and myoblasts at low doses that do not induce mitochondrial accumulation of PINK1. Moreover, both compounds reduce unfolded mitochondrial protein levels, presumably through enhanced PINK1-Parkin signaling. These molecules also mitigate the locomotion defect, reduced ATP production, and disturbed mitochondrial Ca

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: Biological Sciences; Cell Biology; Neuroscience

Conflict of interest statement

Declaration of Interests The authors declare that they have no conflict of interest.

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