- [Nature Reviews Neurology] α-Synuclein pathology as a target in neurodegenerative diseases
- 관리자 |
- 2025-01-06 11:06:57|
- 26
- 2025-01-06 11:06:57|
[Title]
α-Synuclein pathology as a target in neurodegenerative diseases
[Author]
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
1 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3 Adrienne Helis Malvin and Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
4 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
5 Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
6 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9 These authors contributed equally: Hyejin Park, Tae-In Kam.
10These authors jointly supervised this work: Valina L. Dawson, Ted M. Dawson
* corresponding author
[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 modifcations, such as nitration, phosphorylation, ubiquitination, sumoylation and truncation, considering their contributions to neurodegeneration. We also highlight the existence of disease-specifc α-synuclein strains and their mechanisms of pathological spread, and discuss seed amplifcation 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.
α-Synuclein pathology as a target in neurodegenerative diseases
[Author]
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
1 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3 Adrienne Helis Malvin and Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
4 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
5 Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
6 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9 These authors contributed equally: Hyejin Park, Tae-In Kam.
10These authors jointly supervised this work: Valina L. Dawson, Ted M. Dawson
* corresponding author
[Journal]
Nature Reviews Neurology | Volume 21 | January 2025 | 32–47 47[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 modifcations, such as nitration, phosphorylation, ubiquitination, sumoylation and truncation, considering their contributions to neurodegeneration. We also highlight the existence of disease-specifc α-synuclein strains and their mechanisms of pathological spread, and discuss seed amplifcation 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.