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Cynomolgus Monkeys With Spontaneous Type-2-Diabetes-Mellitus-Like Pathology Develop Alpha-Synuclein Alterations Reminiscent of Prodromal Parkinson’s Disease and Related Diseases

Sun, Yan ; Guo, Chuang ; Yuan, Lin ; Li, Wen LU ; Wang, Zhan You ; Yue, Feng and Li, Jia Yi LU (2020) In Frontiers in Neuroscience 14.
Abstract

Available evidence suggests that diabetes mellitus (DM) is a non-genetic risk factor for Parkinson’s disease (PD). PD and DM have shared similarities in pathogenetic mechanisms, including age, environmental factors, inflammatory reaction, and protein aggregation, etc. α-Synuclein is the primary protein component in the protein inclusions in PD, while islet amyloid polypeptide (IAPP) aggregates to form amyloid structures in β cells in type 2 diabetes mellitus (T2DM). Pancreatic and cerebral functions, pancreas and brain α-synuclein deposition as well as striatal alterations, were assessed in spontaneously developed T2DM monkeys and age-matched normal monkeys. We demonstrated increased accumulation, aggregation, and phosphorylation of... (More)

Available evidence suggests that diabetes mellitus (DM) is a non-genetic risk factor for Parkinson’s disease (PD). PD and DM have shared similarities in pathogenetic mechanisms, including age, environmental factors, inflammatory reaction, and protein aggregation, etc. α-Synuclein is the primary protein component in the protein inclusions in PD, while islet amyloid polypeptide (IAPP) aggregates to form amyloid structures in β cells in type 2 diabetes mellitus (T2DM). Pancreatic and cerebral functions, pancreas and brain α-synuclein deposition as well as striatal alterations, were assessed in spontaneously developed T2DM monkeys and age-matched normal monkeys. We demonstrated increased accumulation, aggregation, and phosphorylation of α-synuclein, and IAPP in the pancreatic islets of spontaneously developed T2DM monkeys, compared to the age-matched normal subjects. Double immunofluorescence analyses showed complete overlap between α-synuclein and IAPP in the pancreatic islets. In addition, in T2DM monkeys’ brain, we observed concomitantly increased accumulation and phosphorylation of α-synuclein in the cortex, pre-commissural putamen and dopaminergic neurons in the substantia nigra, which interestingly showed high correlation with levels of fasting plasma glucose (FPG), triglyceride (TG), and high density lipoprotein (HDL). Our data indicates the close association between IAPP and α-synuclein and the potential link between T2DM and PD, which implies that T2DM may facilitate PD disease onset and progress by interfering with the pathological protein aggregation both in the pancreatic islets and the brain.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diabetes mellitus, IAPP, Parkinson’s disease, protein aggregation, synucleinopathies, α-synuclein
in
Frontiers in Neuroscience
volume
14
article number
63
publisher
Frontiers Media S. A.
external identifiers
  • pmid:32116510
  • scopus:85079791163
ISSN
1662-4548
DOI
10.3389/fnins.2020.00063
language
English
LU publication?
yes
id
dcd2150b-7c3f-44ca-ab6c-448a8380d5bc
date added to LUP
2020-03-18 07:35:52
date last changed
2024-04-03 02:58:25
@article{dcd2150b-7c3f-44ca-ab6c-448a8380d5bc,
  abstract     = {{<p>Available evidence suggests that diabetes mellitus (DM) is a non-genetic risk factor for Parkinson’s disease (PD). PD and DM have shared similarities in pathogenetic mechanisms, including age, environmental factors, inflammatory reaction, and protein aggregation, etc. α-Synuclein is the primary protein component in the protein inclusions in PD, while islet amyloid polypeptide (IAPP) aggregates to form amyloid structures in β cells in type 2 diabetes mellitus (T2DM). Pancreatic and cerebral functions, pancreas and brain α-synuclein deposition as well as striatal alterations, were assessed in spontaneously developed T2DM monkeys and age-matched normal monkeys. We demonstrated increased accumulation, aggregation, and phosphorylation of α-synuclein, and IAPP in the pancreatic islets of spontaneously developed T2DM monkeys, compared to the age-matched normal subjects. Double immunofluorescence analyses showed complete overlap between α-synuclein and IAPP in the pancreatic islets. In addition, in T2DM monkeys’ brain, we observed concomitantly increased accumulation and phosphorylation of α-synuclein in the cortex, pre-commissural putamen and dopaminergic neurons in the substantia nigra, which interestingly showed high correlation with levels of fasting plasma glucose (FPG), triglyceride (TG), and high density lipoprotein (HDL). Our data indicates the close association between IAPP and α-synuclein and the potential link between T2DM and PD, which implies that T2DM may facilitate PD disease onset and progress by interfering with the pathological protein aggregation both in the pancreatic islets and the brain.</p>}},
  author       = {{Sun, Yan and Guo, Chuang and Yuan, Lin and Li, Wen and Wang, Zhan You and Yue, Feng and Li, Jia Yi}},
  issn         = {{1662-4548}},
  keywords     = {{diabetes mellitus; IAPP; Parkinson’s disease; protein aggregation; synucleinopathies; α-synuclein}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Neuroscience}},
  title        = {{Cynomolgus Monkeys With Spontaneous Type-2-Diabetes-Mellitus-Like Pathology Develop Alpha-Synuclein Alterations Reminiscent of Prodromal Parkinson’s Disease and Related Diseases}},
  url          = {{http://dx.doi.org/10.3389/fnins.2020.00063}},
  doi          = {{10.3389/fnins.2020.00063}},
  volume       = {{14}},
  year         = {{2020}},
}