Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity

M. Bonin; F. P. Marx; S. Kautzmann; O. Riess; R. Krüger

doi:10.1007/s00702-008-0031-x

Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity

M. Bonin, F. P. Marx, S. Kautzmann, O. Riess, R. Krüger^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

2 Citations (Scopus)

Abstract

Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.

Original language	English
Pages (from-to)	941-958
Number of pages	18
Journal	Journal of Neural Transmission
Volume	115
Issue number	7
DOIs	https://doi.org/10.1007/s00702-008-0031-x
Publication status	Published - Jul 2008
Externally published	Yes

Keywords

Microarray analysis
Neurodegeneration
Parkinson's disease
Synphilin-1
Tumor growth factor beta

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@article{a15ba8d3f256447aa9b231231989473b,

title = "Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity",

abstract = "Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.",

keywords = "Microarray analysis, Neurodegeneration, Parkinson's disease, Synphilin-1, Tumor growth factor beta",

author = "M. Bonin and Marx, \{F. P.\} and S. Kautzmann and O. Riess and R. Kr{\"u}ger",

note = "Funding Information: We thank C. O{\textquoteright}Farrell for providing us with polyclonal synphilin-1 antibodies. This work has been supported by a grant of the Fritz Thyssen Foundation and a grant of the German Research Society (DFG; KR2119/1-1) to R.K.",

year = "2008",

month = jul,

doi = "10.1007/s00702-008-0031-x",

language = "English",

volume = "115",

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journal = "Journal of Neural Transmission",

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T1 - Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity

AU - Bonin, M.

AU - Marx, F. P.

AU - Kautzmann, S.

AU - Riess, O.

AU - Krüger, R.

N1 - Funding Information: We thank C. O’Farrell for providing us with polyclonal synphilin-1 antibodies. This work has been supported by a grant of the Fritz Thyssen Foundation and a grant of the German Research Society (DFG; KR2119/1-1) to R.K.

PY - 2008/7

Y1 - 2008/7

N2 - Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.

AB - Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.

KW - Microarray analysis

KW - Neurodegeneration

KW - Parkinson's disease

KW - Synphilin-1

KW - Tumor growth factor beta

UR - https://www.scopus.com/pages/publications/46649116284

U2 - 10.1007/s00702-008-0031-x

DO - 10.1007/s00702-008-0031-x

M3 - Article

C2 - 18292964

AN - SCOPUS:46649116284

SN - 0300-9564

VL - 115

SP - 941

EP - 958

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

IS - 7

ER -

Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity

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