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

Michael A. Hauser, Yi Ju Li, Hong Xu, Maher A. Noureddine, Yujun S. Shao, Steven R. Gullans, Clemens R. Scherzer, Roderick V. Jensen, Adam C. McLaurin, Jason R. Gibson, Burton L. Scott, Rita M. Jewett, Judith E. Stenger, Donald E. Schmechel, Christine M. Hulette, Jeffery M Vance

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood. Objectives: To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism. Design: Microarray expression analysis of postmortem substantia nigra tissue. Patients: Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects. Main Outcome Measures: Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays. Results: There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism. Conclusions: Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.

Original languageEnglish
Pages (from-to)917-921
Number of pages5
JournalArchives of Neurology
Volume62
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Progressive Supranuclear Palsy
Frontotemporal Dementia
Substantia Nigra
Parkinson Disease
Genes
Parkinsonian Disorders
Mitochondrial Genes
Parkinson's Disease
Profiling
Gene
Ubiquitination
Dopaminergic Neurons
Microarray Analysis
Cluster Analysis
Animal Models
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism. / Hauser, Michael A.; Li, Yi Ju; Xu, Hong; Noureddine, Maher A.; Shao, Yujun S.; Gullans, Steven R.; Scherzer, Clemens R.; Jensen, Roderick V.; McLaurin, Adam C.; Gibson, Jason R.; Scott, Burton L.; Jewett, Rita M.; Stenger, Judith E.; Schmechel, Donald E.; Hulette, Christine M.; Vance, Jeffery M.

In: Archives of Neurology, Vol. 62, No. 6, 01.06.2005, p. 917-921.

Research output: Contribution to journalArticle

Hauser, MA, Li, YJ, Xu, H, Noureddine, MA, Shao, YS, Gullans, SR, Scherzer, CR, Jensen, RV, McLaurin, AC, Gibson, JR, Scott, BL, Jewett, RM, Stenger, JE, Schmechel, DE, Hulette, CM & Vance, JM 2005, 'Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism', Archives of Neurology, vol. 62, no. 6, pp. 917-921. https://doi.org/10.1001/archneur.62.6.917
Hauser, Michael A. ; Li, Yi Ju ; Xu, Hong ; Noureddine, Maher A. ; Shao, Yujun S. ; Gullans, Steven R. ; Scherzer, Clemens R. ; Jensen, Roderick V. ; McLaurin, Adam C. ; Gibson, Jason R. ; Scott, Burton L. ; Jewett, Rita M. ; Stenger, Judith E. ; Schmechel, Donald E. ; Hulette, Christine M. ; Vance, Jeffery M. / Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism. In: Archives of Neurology. 2005 ; Vol. 62, No. 6. pp. 917-921.
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abstract = "Background: Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood. Objectives: To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism. Design: Microarray expression analysis of postmortem substantia nigra tissue. Patients: Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects. Main Outcome Measures: Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays. Results: There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism. Conclusions: Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.",
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T1 - Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism

AU - Hauser, Michael A.

AU - Li, Yi Ju

AU - Xu, Hong

AU - Noureddine, Maher A.

AU - Shao, Yujun S.

AU - Gullans, Steven R.

AU - Scherzer, Clemens R.

AU - Jensen, Roderick V.

AU - McLaurin, Adam C.

AU - Gibson, Jason R.

AU - Scott, Burton L.

AU - Jewett, Rita M.

AU - Stenger, Judith E.

AU - Schmechel, Donald E.

AU - Hulette, Christine M.

AU - Vance, Jeffery M

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Y1 - 2005/6/1

N2 - Background: Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood. Objectives: To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism. Design: Microarray expression analysis of postmortem substantia nigra tissue. Patients: Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects. Main Outcome Measures: Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays. Results: There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism. Conclusions: Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.

AB - Background: Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood. Objectives: To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism. Design: Microarray expression analysis of postmortem substantia nigra tissue. Patients: Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects. Main Outcome Measures: Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays. Results: There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism. Conclusions: Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.

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