Abstract
Synphilin-1 has been identified as an interacting protein of alpha-synuclein, Parkin, and LRRK2, proteins which are mutated in familial forms of Parkinson disease (PD). Subsequently, synphilin-1 has also been shown to be an intrinsic component of Lewy bodies in sporadic PD. In order to elucidate the role of synphilin-1 in the pathogenesis of PD, we generated transgenic mice overexpressing wild-type and mutant (R621C) synphilin-1 driven by a mouse prion protein promoter. Transgenic expression of both wild-type and the R621C variant synphilin-1 resulted in increased dopamine levels of the nigrostriatal system in 3-month-old mice. Furthermore, we found pathological ubiquitin-positive inclusions in cerebellar sections and dark-cell degeneration of Purkinje cells. Both transgenic mouse lines showed significant reduction of motor skill learning and motor performance. These findings suggest a pathological role of overexpressed synphilin-1 in vivo and will help to further elucidate the mechanisms of protein aggregation and neuronal cell death.
Original language | English |
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Pages (from-to) | 107-120 |
Number of pages | 14 |
Journal | Neurogenetics |
Volume | 11 |
Issue number | 1 |
Early online date | 17 Sept 2009 |
DOIs | |
Publication status | Published - 1 Feb 2010 |
Keywords
- animals
- brain
- carrier proteins
- female
- humans
- immunohistochemistry
- male
- mice
- mice, transgenic
- microscopy, electron
- models, genetic
- nerve tissue proteins
- neurotransmitter agents
- positron-emission tomography
- Purkinje cells
- transgenes
- alpha-synuclein
- synphilin-1
- R621C
- mouse model
- Parkinson’s disease
- dark
- cell degeneration
- Purkinje cell
- alpha-synucleinopathies
- neurotransmitter