Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmiss...
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https://www.riss.kr/link?id=A107275372
Kim Changyoun (National Institutes of Health) ; Kwon Somin (National Institutes of Health) ; Iba Michiyo (National Institutes of Health) ; Spencer Brian (University of California) ; Rockenstein Edward (University of California) ; Mante Michael (University of California) ; Adame Anthony (University of California) ; Shin Soo Jean (Seoul National University College of Medicine) ; Fields Jerel A. (University of California) ; Rissman Robert A. (University of California) ; Lee Seung-Jae (Seoul National University College of Medicine) ; Masliah Eliezer (National Institutes of Health)
2021
English
KCI등재,SCOPUS,SCIE
학술저널
1-10(10쪽)
0
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmiss...
Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.
참고문헌 (Reference)
1 김창연, "b1-integrin-dependent migration of microglia response to neuron-released a-synuclein" 생화학분자생물학회 46 : 1-10, 2014
2 McCann, H., "alphaSynucleinopathy phenotypes" 20 : S62-S67, 2014
3 Hansen, C., "alpha-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells" 121 : 715-725, 2011
4 Kakuda, K., "Ultrasonication-based rapid amplification of alpha-synuclein aggregates in cerebrospinal fluid" 9 : 6001-, 2019
5 Manne, S., "Ultrasensitive detection of aggregated alpha-synuclein in glial cells, human cerebrospinal fluid, and brain tissue using the RT-QuIC assay : new high-throughput neuroimmune biomarker assay for Parkinsonian disorders" 14 : 423-435, 2019
6 Stefanova, N., "Toll-like receptor 4 promotes alpha-synuclein clearance and survival of nigral dopaminergic neurons" 179 : 954-963, 2011
7 Fellner, L., "Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia" 61 : 349-360, 2013
8 Dzamko, N., "Toll-like receptor 2 is increased in neurons in Parkinson’s disease brain and may contribute to alpha-synuclein pathology" 133 : 303-319, 2017
9 Van der Perren, A., "The structural differences between patient-derived alpha-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies" 139 : 977-1000, 2020
10 Lashuel, H. A., "The many faces of alphasynuclein: from structure and toxicity to therapeutic target" 14 : 38-48, 2013
1 김창연, "b1-integrin-dependent migration of microglia response to neuron-released a-synuclein" 생화학분자생물학회 46 : 1-10, 2014
2 McCann, H., "alphaSynucleinopathy phenotypes" 20 : S62-S67, 2014
3 Hansen, C., "alpha-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells" 121 : 715-725, 2011
4 Kakuda, K., "Ultrasonication-based rapid amplification of alpha-synuclein aggregates in cerebrospinal fluid" 9 : 6001-, 2019
5 Manne, S., "Ultrasensitive detection of aggregated alpha-synuclein in glial cells, human cerebrospinal fluid, and brain tissue using the RT-QuIC assay : new high-throughput neuroimmune biomarker assay for Parkinsonian disorders" 14 : 423-435, 2019
6 Stefanova, N., "Toll-like receptor 4 promotes alpha-synuclein clearance and survival of nigral dopaminergic neurons" 179 : 954-963, 2011
7 Fellner, L., "Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia" 61 : 349-360, 2013
8 Dzamko, N., "Toll-like receptor 2 is increased in neurons in Parkinson’s disease brain and may contribute to alpha-synuclein pathology" 133 : 303-319, 2017
9 Van der Perren, A., "The structural differences between patient-derived alpha-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies" 139 : 977-1000, 2020
10 Lashuel, H. A., "The many faces of alphasynuclein: from structure and toxicity to therapeutic target" 14 : 38-48, 2013
11 Bendor, J. T., "The function of alpha-synuclein" 79 : 1044-1066, 2013
12 권소민, "Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies" 한국뇌신경과학회 28 (28): 547-553, 2019
13 Shao, Q. H., "TLR4 deficiency has a protective effect in the MPTP/probenecid mouse model of Parkinson’s disease" 40 : 1503-1512, 2019
14 Campolo, M., "TLR4 absence reduces neuroinflammation and inflammasome activation in Parkinson’s diseases in vivo model" 76 : 236-247, 2019
15 Xiaobo Mao, "Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3" American Association for the Advancement of Science (AAAS) 353 (353): 2016
16 Lim, S., "Non-cell-autonomous actions of alphasynuclein : implications in glial synucleinopathies" 169 : 158-171, 2018
17 Guerrero-Ferreira, R., "New insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy" 61 : 89-95, 2020
18 Kim, C., "Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia" 4 : 1562-, 2013
19 Guzman-Martinez, L., "Neuroinflammation as a common feature of neurodegenerative disorders" 10 : 1008-, 2019
20 Zhang, W., "Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alphasynuclein" 55 : 1178-1188, 2007
21 Changyoun Kim, "LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies" American Association for the Advancement of Science (AAAS) 12 (12): 2020
22 Braak, H., "Invited Article : nervous system pathology in sporadic Parkinson disease" 70 : 1916-1925, 2008
23 Desplats, P., "Inclusion formation and neuronal cell death through neuronto-neuron transmission of alpha-synuclein" 106 : 13010-13015, 2009
24 Kim, C., "Immunotherapy targeting Toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating alpha-synuclein transmission and neuroinflammation" 13 : 43-, 2018
25 Kim, C., "Hypoestoxide reduces neuroinflammation and alpha-synuclein accumulation in a mouse model of Parkinson’s disease" 12 : 236-, 2015
26 Fields, J., "Extracellular regulated kinase 1/2 signaling is a critical regulator of interleukin-1beta-mediated astrocyte tissue inhibitor of metalloproteinase-1 expression" 8 : e56891-, 2013
27 Lee, H. J., "Extracellular alpha-synuclein—a novel and crucial factor in Lewy body diseases" 10 : 92-98, 2014
28 Kim, C., "Exposure to bacterial endotoxin generates a distinct strain of alpha-synuclein fibril" 6 : 30891-, 2016
29 Danzer, K. M., "Exosomal cell-to-cell transmission of alpha synuclein oligomers" 7 : 42-, 2012
30 Spencer, B., "ESCRT-mediated uptake and degradation of brain-targeted alpha-synuclein single chain antibody attenuates neuronal degeneration in vivo" 22 : 1753-1767, 2014
31 Masliah, E., "Dopaminergic loss and inclusion body formation in alphasynuclein mice : implications for neurodegenerative disorders" 287 : 1265-1269, 2000
32 Ricardo Guerrero-Ferreira, "Cryo-EM structure of alpha-synuclein fibrils" eLife Sciences Publications, Ltd 7 : 2018
33 Kim, C., "Controlling the mass action of alpha-synuclein in Parkinson’s disease" 107 : 303-316, 2008
34 Lee, H. J., "Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway" 24 : 1888-1896, 2004
35 Lee, H. J., "Clearance and deposition of extracellular alpha-synuclein aggregates in microglia" 372 : 423-428, 2008
36 Ihse, E., "Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type" 7 : 9008-, 2017
37 Alexei A. Surguchev, "Cell Responses to Extracellular α-Synuclein" MDPI AG 24 (24): 305-, 2019
38 Kim, C., "Antagonizing neuronal Toll-like receptor 2 prevents synucleinopathy by activating autophagy" 13 : 771-782, 2015
39 La Vitola, P., "Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2" 69 : 591-602, 2018
Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance
학술지 이력
연월일 | 이력구분 | 이력상세 | 등재구분 |
---|---|---|---|
2023 | 평가예정 | 해외DB학술지평가 신청대상 (해외등재 학술지 평가) | |
2020-01-01 | 평가 | 등재학술지 유지 (해외등재 학술지 평가) | |
2009-09-21 | 학회명변경 | 한글명 : 대한생화학ㆍ분자생물학회 -> 생화학분자생물학회영문명 : Korean Society Of Medical Biochemistry And Molecular Biology -> Korean Society Of Biochemistry And Molecular Biology | |
2008-01-01 | 평가 | SCI 등재 (등재유지) | |
2006-01-01 | 평가 | 등재학술지 유지 (등재유지) | |
2004-01-01 | 평가 | 등재학술지 유지 (등재유지) | |
2001-01-01 | 평가 | 등재학술지 선정 (등재후보2차) | |
1998-07-01 | 평가 | 등재후보학술지 선정 (신규평가) |
학술지 인용정보
기준연도 | WOS-KCI 통합IF(2년) | KCIF(2년) | KCIF(3년) |
---|---|---|---|
2016 | 3.74 | 0.23 | 2.56 |
KCIF(4년) | KCIF(5년) | 중심성지수(3년) | 즉시성지수 |
1.82 | 1.45 | 0.555 | 0.01 |