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Nat. Rev. Neurol., 28 November 2024 | https://doi.org/10.1038/s41582-024-01043-w
α-Synuclein pathology as a target in neurodegenerative diseases
Hyejin Park 1,2,3,4,9, Tae-In Kam 1,2,3,5,9, Valina L. Dawson 1,2,3,6,7,10 & Ted M. Dawson 1,2,3,6,8,10,*
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3Adrienne Helis Malvin and Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
(KAIST), Daejeon, Republic of Korea.
5Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
6Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9These authors contributed equally: Hyejin Park, Tae-In Kam.
10These authors jointly supervised this work: Valina L. Dawson, Ted M. Dawson.
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3Adrienne Helis Malvin and Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
(KAIST), Daejeon, Republic of Korea.
5Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
6Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9These authors contributed equally: Hyejin Park, Tae-In Kam.
10These authors jointly supervised this work: Valina L. Dawson, Ted M. Dawson.
*Corresponding author: correspondence to Ted M. Dawson
Abstract
α-Synuclein misfolds into pathological forms that lead to various neurodegenerative diseases known collectively as α-synucleinopathies. In this Review, we provide a comprehensive overview of pivotal advances in α-synuclein research. We examine structural features and physiological functions of α-synuclein and summarize current insights into key post-translational modifications, such as nitration, phosphorylation, ubiquitination, sumoylation and truncation, considering their contributions to neurodegeneration. We also highlight the existence of disease-specific α-synuclein strains and their mechanisms of pathological spread, and discuss seed amplification assays and PET tracers as emerging diagnostic tools for detecting pathological α-synuclein in clinical settings. We also discuss α-synuclein aggregation and clearance mechanisms, and review cell-autonomous and non-cell-autonomous processes that contribute to neuronal death, including the roles of adaptive and innate immunity in α-synuclein-driven neurodegeneration. Finally, we highlight promising therapeutic approaches that target pathological α-synuclein and provide insights into emerging areas of research.
논문정보
- Review Paper
- 2024년 11월 (BRIC 등록일 2024-11-29)
- 국내+국외 연구진
- 의약학 > 분자세포의학
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