Are synucleinopathies prion-like disorders?
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Sidor
1128-1138
Publikation/Tidskrift/Serie
Lancet Neurology
Volym
Okt
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Lancet Publishing Group
Ämne
- Neurology
Status
Published
Forskningsgrupp
- Molecular Neurobiology
- Neural Plasticity and Repair
ISBN/ISSN/Övrigt
- ISSN: 1474-4465