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Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target

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Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca2+-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.

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Acknowledgements

This work was supported by the Clinical Research Plan of SHDC (No. SHDC2020CR2027B), Shanghai Young Top-notch Talent Support Program, Double Hundred Talents Support Program of Shanghai Jiao Tong University School of Medicine, and the projects sponsored by the development fund for Shanghai talents. The funders had no role in the design and conduction of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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  1. Qinming Zhou, Lu He, and Jin Hu contribute equally to this paper.

Authors and Affiliations

  1. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Qinming Zhou, Lu He, Yining Gao, Dingding Shen, You Ni, Jun Liu & Sheng Chen

  2. Department of Neurology, the First Hospital of Jiaxing & the Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China

    Jin Hu

  3. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226007, China

    Dingding Shen & Sheng Chen

  4. Department of Dermatology, The People’s Hospital of Rushan, Weihai, 264500, China

    Yuening Qin

  5. Department of Neurology, Xinrui Hospital, Wuxi, 214000, China

    Huafeng Liang

  6. Institute of Neurology, Sichuan Academy of Medical Sciences-Sichuan Provincial Hospital, Chengdu, 610072, China

    Weidong Le

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  1. Qinming Zhou
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  2. Lu He
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  8. Huafeng Liang
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  9. Jun Liu
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  10. Weidong Le
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Corresponding authors

Correspondence to Jun Liu, Weidong Le or Sheng Chen.

Ethics declarations

Qinming Zhou, Lu He, Jin Hu, Yining Gao, Dingding Shen, You Ni, Yuening Qin, Huafeng Liang, Jun Liu, Weidong Le, and Sheng Chen declare that they have no conflict of interest. This study was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. We committed to protecting the patients’ privacy and complying with the Helsinki Declaration.

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Zhou, Q., He, L., Hu, J. et al. Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target. Front. Med. 16, 723–735 (2022). https://doi.org/10.1007/s11684-021-0905-y

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  • DOI: https://doi.org/10.1007/s11684-021-0905-y

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