Identification of genes related to Parkinson's disease using expressed sequence tags.
In a search for novel target genes related to Parkinson's disease (PD), two full-length cDNA libraries were constructed from a human normal substantia nigra (SN) and a PD patient's SN. An analysis of the gene expression profiles between them was done using the expressed sequence tags (ESTs) frequency. Data for the differently expressed genes were verified by quantitative real-time RT-PCR, immunohistochemical analysis and a cell death assay. Among the 76 genes identified with a significant difference (P > 0.9), 21 upregulated genes and 13 downregulated genes were confirmed to be differentially expressed in human PD tissues and/or in an MPTP-treated mice model by quantitative real-time RT-PCR. Among those genes, an immunohistochemical analysis using an MPTP mice model for alpha-tubulin including TUBA3 and TUBA6 showed that the protein levels are downregulated, as well as the RNA levels. In addition, MBP, PBP and GNAS were confirmed to accelerate cell death activity, whereas SPP1 and TUBA3 to retard this process. Using an analysis of ESTs frequency, it was possible to identify a large number of genes related to human PD. These new genes, MBP, PBP, GNAS, SPP1 and TUBA3 in particular, represent potential biomarkers for PD and could serve as useful targets for elucidating the molecular mechanisms associated with PD.
Kim
Jeong-Min
JM
Laboratory of Human Genomics, Genome Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon, Korea.
Lee
Kyu-Hwa
KH
Jeon
Yeo-Jin
YJ
Oh
Jung-Hwa
JH
Jeong
So-Young
SY
Song
In-Sung
IS
Kim
Jin-Man
JM
Lee
Dong-Seok
DS
Kim
Nam-Soon
NS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016923:Cell Death; D002864:Chromogranins; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D020224:Expressed Sequence Tags / Q000737:chemistry*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism; D015723:Gene Library; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000009:adverse effects; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D002864:Chromogranins; D003598:Cytoskeletal Proteins; C482331:DNMBP protein, human; C485840:DOCK3 protein, human; D020662:Guanine Nucleotide Exchange Factors; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C506895:SPP1 protein, human; D014157:Transcription Factors; D053495:Osteopontin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs