PMID- 18292964
OWN - NLM
STAT- MEDLINE
DCOM- 20081105
LR  - 20211020
IS  - 0300-9564 (Print)
IS  - 0300-9564 (Linking)
VI  - 115
IP  - 7
DP  - 2008 Jul
TI  - Microarray expression analysis reveals genetic pathways implicated in C621 
      synphilin-1-mediated toxicity.
PG  - 941-58
LID - 10.1007/s00702-008-0031-x [doi]
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.
FAU - Bonin, M
AU  - Bonin M
AD  - Department of Medical Genetics, Microarray Facility, University of Tubingen, 
      Tubingen, Germany.
FAU - Marx, F P
AU  - Marx FP
FAU - Kautzmann, S
AU  - Kautzmann S
FAU - Riess, O
AU  - Riess O
FAU - Kruger, R
AU  - Kruger R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080222
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Carrier Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SNCAIP protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 94ZLA3W45F (Arginine)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Arginine/*genetics
MH  - Carrier Proteins/*genetics
MH  - Cell Line, Transformed
MH  - Cysteine/*genetics
MH  - Gene Expression Regulation/*genetics
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Mutation/*genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Signal Transduction/*genetics
MH  - Transfection/methods
MH  - Transforming Growth Factor beta/genetics/metabolism
EDAT- 2008/02/23 09:00
MHDA- 2008/11/06 09:00
CRDT- 2008/02/23 09:00
PHST- 2007/10/25 00:00 [received]
PHST- 2008/02/01 00:00 [accepted]
PHST- 2008/02/23 09:00 [pubmed]
PHST- 2008/11/06 09:00 [medline]
PHST- 2008/02/23 09:00 [entrez]
AID - 10.1007/s00702-008-0031-x [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2008 Jul;115(7):941-58. doi: 10.1007/s00702-008-0031-x. 
      Epub 2008 Feb 22.