PMID- 36621149
OWN - NLM
STAT- MEDLINE
DCOM- 20230203
LR  - 20230301
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 644
DP  - 2023 Feb 12
TI  - Extracellular transportation of alpha-synuclein by HLA class II molecules.
PG  - 25-33
LID - S0006-291X(22)01761-2 [pii]
LID - 10.1016/j.bbrc.2022.12.082 [doi]
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the 
      progressive accumulation of alpha-synuclein aggregates in form of Lewy bodies. 
      Genome-wide association studies have revealed that human leukocyte antigen (HLA) 
      class II is a PD-associated gene, although the mechanisms linking HLA class II 
      and PD remain elusive. Here, we identified a novel function of HLA class II in 
      the transport of intracellular alpha-synuclein to the outside of cells. HLA class II 
      molecules and alpha-synuclein formed complexes and moved to the cell surface at 
      various degrees among HLA-DR alleles. HLA-DR with a DRB5 *01:01 allele, a putative 
      PD-risk allele, substantially translocated normal and conformationally abnormal 
      alpha-synuclein to the cell surface and extracellular vesicles. alpha-Synuclein/HLA class 
      II complexes were found in A2058 melanoma cells, which express intrinsic 
      alpha-synuclein and HLA-DR with DRB5 *01:01. Our findings will expand our knowledge of 
      unconventional HLA class II function from autoimmune diseases to 
      neurodegenerative disorders, shedding light on the association between the 
      GWAS-prioritized PD-risk gene HLA-DR and alpha-synuclein.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Ozono, Tatsuhiko
AU  - Ozono T
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan; Laboratory of Immunochemistry, 
      Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, 
      Osaka, 565-0871, Japan.
FAU - Kimura, Yasuyoshi
AU  - Kimura Y
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Suenaga, Tadahiro
AU  - Suenaga T
AD  - Laboratory of Immunochemistry, Immunology Frontier Research Center, Osaka 
      University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of 
      Immunochemistry, Research Institute for Microbial Diseases, Osaka University, 3-1 
      Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Immunology, Kitasato 
      University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 
      252-0374, Japan.
FAU - Beck, Goichi
AU  - Beck G
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Jinno, Jyunki
AU  - Jinno J
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Aguirre, Cesar
AU  - Aguirre C
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Ikenaka, Kensuke
AU  - Ikenaka K
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Krainc, Dimitri
AU  - Krainc D
AD  - Department of Neurology, Northwestern University Feinberg School of Medicine, 
      Chicago, IL, USA.
FAU - Mochizuki, Hideki
AU  - Mochizuki H
AD  - Department of Neurology, Osaka University Graduate School of Medicine, 2-2, 
      Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: 
      hmochizuki@neurol.med.osaka-u.ac.jp.
FAU - Arase, Hisashi
AU  - Arase H
AD  - Laboratory of Immunochemistry, Immunology Frontier Research Center, Osaka 
      University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of 
      Immunochemistry, Research Institute for Microbial Diseases, Osaka University, 3-1 
      Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: 
      arase@biken.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221231
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (alpha-Synuclein)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - *alpha-Synuclein/genetics/metabolism
MH  - Genome-Wide Association Study
MH  - *Parkinson Disease/genetics/metabolism
MH  - Lewy Bodies/metabolism
MH  - HLA Antigens
OTO - NOTNLM
OT  - Extracellular transport
OT  - HLA class II
OT  - HLA-DRB5 *01:01
OT  - Parkinson's disease
OT  - alpha-Synuclein
EDAT- 2023/01/10 06:00
MHDA- 2023/02/04 06:00
CRDT- 2023/01/09 04:35
PHST- 2022/12/17 00:00 [received]
PHST- 2022/12/28 00:00 [accepted]
PHST- 2023/01/10 06:00 [pubmed]
PHST- 2023/02/04 06:00 [medline]
PHST- 2023/01/09 04:35 [entrez]
AID - S0006-291X(22)01761-2 [pii]
AID - 10.1016/j.bbrc.2022.12.082 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2023 Feb 12;644:25-33. doi: 
      10.1016/j.bbrc.2022.12.082. Epub 2022 Dec 31.