A deadly spread: cellular mechanisms of α-synuclein transfer.
Författare
Summary, in English
Classically, Parkinson's disease (PD) is linked to dopamine neuron death in the substantia nigra pars compacta. Intracytoplasmic protein inclusions named Lewy bodies, and corresponding Lewy neurites found in neuronal processes, are also key features of the degenerative process in the substantia nigra. The molecular mechanisms by which substantia nigra dopamine neurons die and whether the Lewy pathology is directly involved in the cell death pathway are open questions. More recently, it has become apparent that Lewy pathology gradually involves greater parts of the PD brain and is widespread in late stages. In this review, we first discuss the role of misfolded α-synuclein protein, which is the main constituent of Lewy bodies, in the pathogenesis of PD. We then describe recent evidence that α-synuclein might transfer between cells in PD brains. We discuss in detail the possible molecular mechanisms underlying the proposed propagation and the likely consequences for cells that take up α-synuclein. Finally, we focus on aspects of the pathogenic process that could be targeted with new pharmaceutical therapies or used to develop biomarkers for early PD detection.Cell Death and Differentiation advance online publication, 13 May 2011; doi:10.1038/cdd.2011.53.
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
1425-1433
Publikation/Tidskrift/Serie
Cell Death and Differentiation
Volym
18
Issue
9
Fulltext
- Available as PDF - 18 MB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Neurosciences
Nyckelord
- prion-like
- Parkinson's disease
- alpha-synuclein
- seeding
- aggregation
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1350-9047