Seung‐Jae Lee

Seoul National University

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Co-Authors

He-Jin Lee

Konkuk University

Eun-Jin Bae

Seoul National University

Eliezer Masliah

University of California, San Diego

Changyoun Kim

University of California, San Diego

Pyo‐Jam Park

Konkuk University

Byung Chul Jung

University of California, Berkeley

Jun Sung Lee

Gangnam Severance Hospital

Eun‐Kyung Kim

Dong-A University

Jin-Woo Hwang

Dankook University

Sang-Ho Moon

Sookmyung Women's University

Cooperative Institutions

Weatherford College

160

Seoul National University

147

Agruicultural Research Institute

111

Ames National Laboratory

111

Konkuk University

100

Boonton Public Schools

Yonsei University

Harvard University

Korea University

Pohang University of Science and Technology

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Cell Biology of α-Synuclein: Implications in Parkinson’s Disease and Other Lewy Body Diseases

Springer eBooks (2007)

Seung‐Jae Lee Yoon Suk Kim

Lewy body

Axoplasmic transport

Inclusion bodies

10.1007/978-0-387-36534-3_5

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Citations (0)

Multiple non-cell autonomous actions of α-synuclein in neurodegenerative diseases

Cell Cycle (2010)

Seung‐Jae Lee He-Jin Lee Eliezer Masliah

"Multiple non-cell autonomous actions of α-synuclein in neurodegenerative diseases." Cell Cycle, 9(14), pp. 2696–2697

10.4161/cc.9.14.12590

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Citations (4)

Changes in oligodendroglial subpopulations in Parkinson’s disease

Molecular Brain (2023)

Eun-Jin Bae Dayana Pérez-Acuña Ka Hyun Rhee Seung‐Jae Lee

Parkinson's disease (PD) is characterized by a selective loss of dopaminergic neurons. While most research on PD conducted to date has focused on neurons and, to a certain extent, glia, few studies have investigated changes in oligodendroglia. Here, we investigated the heterogeneity of oligodendrocytes from PD patients compared with those of control cases by analyzing single-nuclei transcriptomes. These analyses revealed the presence of distinct oligodendrocyte populations in PD patients indicative of corresponding variations in molecular features, notably including activation of inflammatory responses, response to protein folding stress, and myelination abnormalities. We confirmed myelination abnormalities in an α-synuclein preformed fibril-injection mouse model of PD. These results suggest that oligodendrocytes acquire disease-associated phenotypes in PD and may contribute to the accompanying neurodegeneration.

Proteostasis

10.1186/s13041-023-01055-5

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Citations (16)

PARK1 and α-Synuclein

Elsevier eBooks (2003)

J. William Langston Lawrence I. Golbe Seung‐Jae Lee

10.1016/b978-012566652-7/50029-0

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LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies

Science Translational Medicine (2020)

Changyoun Kim A Beilina Nathan Smith Yan Li Minhyung Kim

Synucleinopathies are neurodegenerative disorders characterized by abnormal α-synuclein deposition that include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. The pathology of these conditions also includes neuronal loss and neuroinflammation. Neuron-released α-synuclein has been shown to induce neurotoxic, proinflammatory microglial responses through Toll-like receptor 2, but the molecular mechanisms involved are poorly understood. Here, we show that leucine-rich repeat kinase 2 (LRRK2) plays a critical role in the activation of microglia by extracellular α-synuclein. Exposure to α-synuclein was found to enhance LRRK2 phosphorylation and activity in mouse primary microglia. Furthermore, genetic and pharmacological inhibition of LRRK2 markedly diminished α-synuclein-mediated microglial neurotoxicity via lowering of tumor necrosis factor-α and interleukin-6 expression in mouse cultures. We determined that LRRK2 promoted a neuroinflammatory cascade by selectively phosphorylating and inducing nuclear translocation of the immune transcription factor nuclear factor of activated T cells, cytoplasmic 2 (NFATc2). NFATc2 activation was seen in patients with synucleinopathies and in a mouse model of synucleinopathy, where administration of an LRRK2 pharmacological inhibitor restored motor behavioral deficits. Our results suggest that modulation of LRRK2 and its downstream signaling mediator NFATc2 might be therapeutic targets for treating synucleinopathies.

Synucleinopathies

LRRK2

Neurotoxicity

Proinflammatory cytokine

10.1126/scitranslmed.aay0399

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Citations (60)

Non-cell-autonomous actions of α-synuclein: Implications in glial synucleinopathies

Progress in Neurobiology (2018)

Somin Lim Han‐Joon Kim Dong‐Kyu Kim Seung‐Jae Lee

Synucleinopathies

Cell type

10.1016/j.pneurobio.2018.06.010

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Citations (25)

Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy

Neurobiology of Disease (2017)

Omar M. A. El‐Agnaf Cassia Overk Edward Rockenstein Michael Mante Jazmin Florio

Synucleinopathies

Amyloid (mycology)

10.1016/j.nbd.2017.05.002

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Citations (73)

Amplification of distinct α-synuclein fibril conformers through protein misfolding cyclic amplification

Experimental & Molecular Medicine (2017)

Byung Chul Jung Yoon-Ju Lim Eun-Jin Bae Jun Sung Lee Min Sun Choi

Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease. Using a technique known as protein misfolding cyclic amplification, originally developed for amplifying prions, we established a procedure through which the amplification of α-synuclein fibrils is possible. With a trace amount of seeds, we succeeded in amplifying α-synuclein fibrils. The replication of the seeds was faithful in terms of conformation even after multiple rounds of cyclic amplification. Moreover, two transgenic mouse strains each representing a distinct synucleinopathy were used to investigate different conformers by using this technique. The amplified α-synuclein fibrils derived from the tissue extracts of these two strains led to the production of two different fibril conformers with distinct proteinase K digestion profiles. Together, our results demonstrated that a trace amount of α-synuclein fibrils in tissue extracts could be amplified with their conformations conserved. This procedure should be useful in amplifying α-synuclein fibrils from the brains and body fluids of patients afflicted with synucleinopathies and may serve as a potential diagnostic tool for Parkinson disease and other synucleinopathies. A method to copy fibrous protein structures associated with neurodegenerative diseases could aid diagnosis and basic research. Specific protein molecules fold and aggregate to form deposits known as amyloid fibrils in brain cells in conditions such as Alzheimer's and Parkinson's diseases. Studying these misfolded proteins in patients' brains or animal models has been hampered by difficulties in obtaining adequate supplies. Seung-Jae Lee and colleagues at Seoul National University, with co-workers elsewhere in Korea and in the USA, have developed a way to use a small sample of one such protein as a "seed" that can be amplified into larger quantities of protein molecules with the same disease-linked folding pattern as the seed. They demonstrated their method using a protein found in patients with Parkinson's disease. Application to other diseases could also be explored.

Conformational isomerism

Synucleinopathies

Amyloid (mycology)

10.1038/emm.2017.1

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Citations (46)

CRISPR-based identification of N-terminal acetylation in synucleinopathies

Trends in Neurosciences (2024)

Eun-Jin Bae Seung‐Jae Lee

Synucleinopathies

Identification

10.1016/j.tins.2024.03.006

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Citations (0)

Effect of range resolution in the analysis of X-band sea clutter at low grazing angles

Journal of Electromagnetic Waves and Applications (2019)

Ji-Eun Kim Sang-Min Lee Chan-Hong Kim Young-Soo Kim Seung‐Jae Lee

Analyses of sea spikes are presented for data measured at low grazing angles using a high-resolution X-band radar. To investigate the spikiness of sea clutter at different range resolutions, several analyses and statistical modelling were applied to measured sea clutter data with different resolutions and polarizations. The results show that the spikiness of sea clutter increases as the range resolution becomes finer.

Radar horizon

10.1080/09205071.2019.1688690

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Citations (2)