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Pathogenesis of Parkinson’s disease: from hints from monogenic familial PD to biomarkers

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Twenty-five years have passed since the causative gene for familial Parkinson's disease (PD), Parkin (now PRKN), was identified in 1998; PRKN is the most common causative gene in young-onset PD. Parkin encodes a ubiquitin-protein ligase, and Parkin is involved in mitophagy, a type of macroautophagy, in concert with PTEN-induced kinase 1 (PINK1). Both gene products are also involved in mitochondrial quality control. Among the many genetic PD-causing genes discovered, discovering PRKN as a cause of juvenile-onset PD has significantly impacted other neurodegenerative disorders. This is because the involvement of proteolytic systems has been suggested as a common mechanism in neurodegenerative diseases in which inclusion body formation is observed. The discovery of the participation of PRKN in PD has brought attention to the involvement of the proteolytic system in neurodegenerative diseases. Our research group has successfully isolated and identified CHCHD2, which is involved in the mitochondrial electron transfer system, and prosaposin (PSAP), which is involved in the lysosomal system, in this Parkin mechanism. Hereditary PD is undoubtedly an essential clue to solitary PD, and at least 25 or so genes and loci have been reported so far. This number of genes indicates that PD is a very diverse group of diseases. Currently, the diagnosis of PD is based on clinical symptoms and imaging studies. Although highly accurate diagnostic criteria have been published, early diagnosis is becoming increasingly important in treatment strategies for neurodegenerative diseases. Here, we also describe biomarkers that our group is working on.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan

    Nobutaka Hattori, Manabu Funayama, Yuzuru Imai & Taku Hatano

  2. Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan

    Nobutaka Hattori & Manabu Funayama

  3. Center for Genomic and Regenerative Medicine, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan

    Nobutaka Hattori & Manabu Funayama

  4. Department of Research for Parkinson’s Disease, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan

    Nobutaka Hattori & Yuzuru Imai

  5. Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, 2-1-Hirosawa, Wako-shi, Saitama, 351-0198, Japan

    Nobutaka Hattori

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Hattori, N., Funayama, M., Imai, Y. et al. Pathogenesis of Parkinson’s disease: from hints from monogenic familial PD to biomarkers. J Neural Transm (2024). https://doi.org/10.1007/s00702-024-02747-5

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