Advanced

Are synucleinopathies prion-like disorders?

Angot, Elodie LU ; Steiner, Jennifer LU ; Hansen, Christian LU ; Li, Jia-Yi LU and Brundin, Patrik LU (2010) In Lancet Neurology Okt. p.1128-1138
Abstract
A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of α-synuclein that gradually engage increasing parts of the nervous system. The pathogenetic mechanisms underlying these neurodegenerative disorders, however, are unknown. Several studies have highlighted similarities between classic prion diseases and these neurological proteinopathies. Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons. These results... (More)
A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of α-synuclein that gradually engage increasing parts of the nervous system. The pathogenetic mechanisms underlying these neurodegenerative disorders, however, are unknown. Several studies have highlighted similarities between classic prion diseases and these neurological proteinopathies. Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons. These results and others have led to the hypothesis that a prion-like mechanism might underlie progression of synucleinopathy within the nervous system. We review experimental findings showing that misfolded α-synuclein can transfer between cells and, once transferred into a new cell, can act as a seed that recruits endogenous α-synuclein, leading to formation of larger aggregates. This model suggests that strategies aimed at prevention of cell-to-cell transfer of α-synuclein could retard progression of symptoms in Parkinson's disease and other synucleinopathies. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Lancet Neurology
volume
Okt
pages
1128 - 1138
publisher
Lancet Ltd
external identifiers
  • wos:000284246800021
  • pmid:20846907
  • scopus:77957939093
ISSN
1474-4465
DOI
10.1016/S1474-4422(10)70213-1
language
English
LU publication?
yes
id
1dfbd49d-a09a-468f-9d79-c67a4dad8dd8 (old id 1688149)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20846907?dopt=Abstract
date added to LUP
2010-10-06 07:37:42
date last changed
2018-05-29 11:16:34
@article{1dfbd49d-a09a-468f-9d79-c67a4dad8dd8,
  abstract     = {A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of α-synuclein that gradually engage increasing parts of the nervous system. The pathogenetic mechanisms underlying these neurodegenerative disorders, however, are unknown. Several studies have highlighted similarities between classic prion diseases and these neurological proteinopathies. Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons. These results and others have led to the hypothesis that a prion-like mechanism might underlie progression of synucleinopathy within the nervous system. We review experimental findings showing that misfolded α-synuclein can transfer between cells and, once transferred into a new cell, can act as a seed that recruits endogenous α-synuclein, leading to formation of larger aggregates. This model suggests that strategies aimed at prevention of cell-to-cell transfer of α-synuclein could retard progression of symptoms in Parkinson's disease and other synucleinopathies.},
  author       = {Angot, Elodie and Steiner, Jennifer and Hansen, Christian and Li, Jia-Yi and Brundin, Patrik},
  issn         = {1474-4465},
  language     = {eng},
  pages        = {1128--1138},
  publisher    = {Lancet Ltd},
  series       = {Lancet Neurology},
  title        = {Are synucleinopathies prion-like disorders?},
  url          = {http://dx.doi.org/10.1016/S1474-4422(10)70213-1},
  volume       = {Okt},
  year         = {2010},
}