PMID- 37150314
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20231116
IS  - 1873-5118 (Electronic)
IS  - 0301-0082 (Linking)
VI  - 226
DP  - 2023 Jul
TI  - Islet amyloid polypeptide triggers alpha-synuclein pathology in Parkinson's disease.
PG  - 102462
LID - S0301-0082(23)00062-X [pii]
LID - 10.1016/j.pneurobio.2023.102462 [doi]
AB  - Pathologic aggregation and prion-like propagation of alpha-synuclein (alpha-syn) are the 
      hallmarks of Parkinson's disease (PD). Emerging evidence shows that type 2 
      diabetes mellitus (T2DM) is a risk factor for PD. Interestingly, T2DM is 
      characterized by the amyloid deposition of islet amyloid polypeptide (IAPP) in 
      the pancreas. Although T2DM and PD share pathological similarities, the 
      underlying molecular mechanisms bridging these two diseases remain unknown. Here, 
      we report that IAPP co-deposits with alpha-syn in the brains of PD patients. IAPP 
      interacts with alpha-syn and accelerates its aggregation. In addition, the 
      IAPP-seeded alpha-syn fibrils show enhanced seeding activity and neurotoxicity 
      compared with pure alpha-syn fibrils in vitro and in vivo. Strikingly, intravenous 
      injection of IAPP fibrils into alpha-syn A53T transgenic mice or human SNCA 
      transgenic mice accelerated the aggregation of alpha-syn and PD-like motor deficits. 
      Taken together, these findings support that IAPP acts as a trigger of alpha-syn 
      pathology in PD, and provide a mechanistic explanation for the increased risk and 
      faster progression of PD in patients with T2DM.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Meng, Lanxia
AU  - Meng L
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Li, Yiming
AU  - Li Y
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Liu, Congcong
AU  - Liu C
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Zhang, Guoxin
AU  - Zhang G
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Chen, Jiehui
AU  - Chen J
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Xiong, Min
AU  - Xiong M
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Pan, Lina
AU  - Pan L
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Zhang, Xingyu
AU  - Zhang X
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Chen, Guiqin
AU  - Chen G
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China; Department of Pathology and Laboratory Medicine, Emory University School 
      of Medicine, Atlanta, GA 30322, USA.
FAU - Xiong, Jing
AU  - Xiong J
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China; Department of Pathology and Laboratory Medicine, Emory University School 
      of Medicine, Atlanta, GA 30322, USA.
FAU - Liu, Chaoyang
AU  - Liu C
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China; Research Center for Environment and Health, Zhongnan University of 
      Economics and Law, Wuhan 430073, China.
FAU - Xu, Ximing
AU  - Xu X
AD  - Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
FAU - Bu, Lihong
AU  - Bu L
AD  - PET-CT/MRI Center, Faculty of Radiology and Nuclear Medicine, Renmin Hospital of 
      Wuhan University, Wuhan 430060, China.
FAU - Zhang, Zhaohui
AU  - Zhang Z
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Zhang, Zhentao
AU  - Zhang Z
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China. Electronic address: Zhentaozhang@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230505
PL  - England
TA  - Prog Neurobiol
JT  - Progress in neurobiology
JID - 0370121
RN  - 0 (alpha-Synuclein)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Amyloid)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *Parkinson Disease/pathology
MH  - alpha-Synuclein
MH  - Islet Amyloid Polypeptide
MH  - *Diabetes Mellitus, Type 2
MH  - Mice, Transgenic
MH  - Amyloid/chemistry
OTO - NOTNLM
OT  - Aggregation
OT  - Cross-seeding
OT  - Neurodegeneration
OT  - Synucleinopathy
OT  - Type 2 diabetes mellitus (T2DM)
COIS- Declaration of Competing Interest The authors report no competing interests.
EDAT- 2023/05/08 00:41
MHDA- 2023/06/12 06:42
CRDT- 2023/05/07 19:25
PHST- 2022/12/06 00:00 [received]
PHST- 2023/03/28 00:00 [revised]
PHST- 2023/05/01 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/05/08 00:41 [pubmed]
PHST- 2023/05/07 19:25 [entrez]
AID - S0301-0082(23)00062-X [pii]
AID - 10.1016/j.pneurobio.2023.102462 [doi]
PST - ppublish
SO  - Prog Neurobiol. 2023 Jul;226:102462. doi: 10.1016/j.pneurobio.2023.102462. Epub 
      2023 May 5.