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Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson’s Disease

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Abstract

Parkinson’s disease is the second most prevalent neurodegenerative disease and contributes significantly to morbidity globally. Currently, no disease-modifying therapies exist to combat this disorder. Insights from the molecular and cellular pathobiology of the disease seems to indicate promising therapeutic targets. The parkin protein has been extensively studied for its role in autosomal recessive Parkinson’s disease and, more recently, its role in sporadic Parkinson’s disease. Parkin is an E3 ubiquitin ligase that plays a prominent role in mitochondrial quality control, mitochondrial-dependent cell death pathways, and other diverse functions. Understanding the numerous roles of parkin has introduced many new possibilities for therapeutic modalities in treating both autosomal recessive Parkinson’s disease and sporadic Parkinson’s disease. In this article, we review parkin biology with an emphasis on mitochondrial-related functions and propose novel, potentially disease-modifying therapeutic approaches for treating this debilitating condition.

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Acknowledgments

The authors thank Noelle Burgess for assistance in creating the figures.

Author information

Author notes

  1. Valina L. Dawson and Ted M. Dawson contributed equally to the article.

Authors and Affiliations

  1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Jaimin Patel, Nikhil Panicker, Valina L. Dawson & Ted M. Dawson

  2. Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jaimin Patel

  3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Nikhil Panicker, Valina L. Dawson & Ted M. Dawson

  4. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Valina L. Dawson & Ted M. Dawson

  5. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Valina L. Dawson

  6. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ted M. Dawson

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  1. Jaimin Patel
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Correspondence to Valina L. Dawson or Ted M. Dawson.

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Funding

This work was supported by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS38377, NS097049, and NS102035), and the JPB Foundation.

Conflicts of interest/competing interests

Consulting: T.M.D has received personal compensation for consulting with Sun Pharma Advanced Research Company; T.M.D. is a consultant for Mitokinin; T.M.D. and V.L.D. are consultants to Inhibikase Therapeutics Inc.; T.M.D. serves on the Board of Directors and is compensated for his roles as a consultant and interim Chief Scientific Officer of Valted Seq Inc.; V.L.D. serves on the Board of Directors and is compensated for her role as interim Chief Executive Officer of Valted Seq Inc. T.M.D. was a paid consultant and advisory board member to DONG-A ST; T.M.D. and V.L.D. received personal compensation for consulting and serving on a scientific advisory board with Hopstem, Inc. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Stock Ownership: T.M.D. owns stock options in American Gene Technologies International Inc.; T.M.D owns stock and stock options in Mitokinin; T.M.D. and V.L.D. own stock options in Inhibikase Therapeutics Inc.; T.M.D. and V.L.D. are founders of Valted, LLC and holds an ownership equity interest in the company. T.M.D. and V.L.D. are inventors of technology of Neuraly, Inc. that has optioned from Johns Hopkins University. T.M.D. and V.L.D. are founders of, and holds shares of stock options as well as equity in, Neuraly, Inc., which is now a subsidiary of D & D Pharmatech; T.M.D. and V.L.D. holds shares of stock options as well as equity in D & D Pharmatech; T.M.D. and V.L.D. are founders of and hold equity in Valted Seq Inc.; these arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. J.P. and N.P. have no conflicts of interest or disclosures.

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JP reviewed the literature, conceptualized and developed the original draft of the manuscript, and participated in reviewing as well as editing the manuscript. NP participated in the literature searching and conceptualizing, reviewing, and editing the manuscript. TMD and VLD both participated in reviewing, editing, and conceptualizing the manuscript. All authors have read and approved the final version of the manuscript, and they agree to be accountable for the work.

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Patel, J., Panicker, N., Dawson, V.L. et al. Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson’s Disease. CNS Drugs 36, 1249–1267 (2022). https://doi.org/10.1007/s40263-022-00973-7

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