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Literature DB >> 16344956

Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.

L B Moran¹, D C Duke, M Deprez, D T Dexter, R K B Pearce, M B Graeber.

Abstract

We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra. In addition, the superior frontal cortex was analyzed in a subset of the same cases. DNA oligonucleotide microarrays were employed, which provide whole human genome coverage. A total of 570 genes were found to be differentially regulated at a high level of significance. A large number of differentially regulated expressed sequence tags were also identified. Levels of mRNA sequences encoded by genes of key interest were validated by means of quantitative real-time polymerase chain reaction (PCR). Comparing three different normalization procedures, results based on the recently published GeneChip Robust Multi Array algorithm were found to be the most accurate predictor of real-time PCR results. Several new candidate genes which map to PARK loci are reported. In addition, the DNAJ family of chaperones is discussed in the context of Parkinson's disease pathogenesis.

Entities: Chemical

Mesh：

Year: 2006 PMID： 16344956 DOI： 10.1007/s10048-005-0020-2

Source DB: PubMed Journal: Neurogenetics ISSN： 1364-6745 Impact factor: 2.660

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Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.

Review 1. A role for Rad23 proteins in 26S proteasome-dependent protein degradation?

2. Nigral neurons are likely to die of a mechanism other than classical apoptosis in Parkinson's disease.

3. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.

4. On the question of apoptosis in the parkinsonian substantia nigra.

5. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.

6. Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism.

7. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.

8. Identification of risk and age-at-onset genes on chromosome 1p in Parkinson disease.

9. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.

10. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.

1. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

2. Nociceptin/Orphanin FQ Inhibits the Survival and Axon Growth of Midbrain Dopaminergic Neurons Through a p38-MAPK Dependent Mechanism.

3. DEGAS: de novo discovery of dysregulated pathways in human diseases.

4. Guilt by rewiring: gene prioritization through network rewiring in genome wide association studies.

5. Semantic relations for interpreting DNA microarray data.

6. AlzBase: an Integrative Database for Gene Dysregulation in Alzheimer's Disease.

7. Parkinson's Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning.

8. Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology.

9. One Decade Later: What has Gene Expression Profiling Told us About Neuronal Cell Types, Brain Function and Disease?

10. A cross-study transcriptional analysis of Parkinson's disease.