ArticleJournal of neural transmission (Vienna, Austria : 1996)2012
A53T-alpha-synuclein-overexpression in the mouse nigrostriatal pathway leads to early increase of 14-3-3 epsilon and late increase of GFAP.
Article in Journal of neural transmission (Vienna, Austria : 1996), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 35 citations in OpenAlex.
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- Development of Highly Multiplex Targeted Proteomics Assays in Biofluids Using a Nominal Mass Ion Trap Mass Spectrometer.Molecular & cellular proteomics : MCP · 2026Article
- Enteric glia, neuropeptides, and Parkinson's: impacts of calcitonin gene-related peptide on gut alpha synuclein.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow-derived stromal cells.Journal of cellular and molecular medicine · 2020Article
- Article
- SerThr-PhosphoProteome of Brain from Aged PINK1-KO+A53T-SNCA Mice Reveals pT1928-MAP1B and pS3781-ANK2 Deficits, as Hub between Autophagy and Synapse Changes.International journal of molecular sciences · 2019Article
- Impaired Photic Entrainment of Spontaneous Locomotor Activity in Mice Overexpressing Human Mutant α-Synuclein.International journal of molecular sciences · 2018Article
- Methyl-Arginine Profile of Brain from Aged PINK1-KO+A53T-SNCA Mice Suggests Altered Mitochondrial Biogenesis.Parkinson's disease · 2016Article
- Identification of chaperones in a MPPAmerican journal of translational research · 2016Article
- A Genetic Mouse Model of Parkinson's Disease Shows Involuntary Movements and Increased Postsynaptic Sensitivity to Apomorphine.Molecular neurobiology · 2015Article
- Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha-Synuclein Pathology.Molecular neurobiology · 2015Article
- Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression.Human molecular genetics · 2015Article
- α-Synuclein Misfolding Versus Aggregation Relevance to Parkinson's Disease: Critical Assessment and Modeling.Molecular neurobiology · 2015Review
- Transglutaminase 2 exacerbates α-synuclein toxicity in mice and yeast.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- 14-3-3 Proteins in the regulation of rotenone-induced neurotoxicity might be via its isoform 14-3-3epsilon's involvement in autophagy.Cellular and molecular neurobiology · 2013Article
- Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.PloS one · 2013Article
- Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.PloS one · 2012Article
- Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.PloS one · 2012Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder frequent at old age characterized by atrophy of the nigrostriatal projection. Overexpression and A53T-mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are known to cause early-onset autosomal dominant PD. We previously generated mice with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in dopaminergic substantia nigra neurons as a model of early PD. To elucidate the early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic nerve terminals in the striatum, we now investigated expression profiles of young and old mice using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2 downregulated. Mice before the onset of motor anomalies showed an upregulation of the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well as altered levels of chaperones, vesicle trafficking and bioenergetics proteins. In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation and 14-3-3 upregulation for the epsilon isoform, and also detected significant eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD brains. They act as chaperones in signaling, dopamine synthesis and stress response. Thus, their early dysregulation probably reflects a response to alpha-synuclein toxicity.
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