Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology.
Frontotemporal lobar degeneration (FTLD) is the most common cause of dementia with pre-senile onset, accounting for as many as 20% of cases. A common subset of FTLD cases is characterized by the presence of ubiquitinated inclusions in vulnerable neurons (FTLD-U). While the pathophysiological mechani...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-04-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fneur.2011.00024/full |
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| author | Yair M. Gozal Yair M. Gozal Yair M. Gozal Eric B. Dammer Eric B. Dammer Eric B. Dammer Duc M. Duong Duc M. Duong Duc M. Duong Dongmei eCheng Dongmei eCheng Dongmei eCheng Marla eGearing Marla eGearing Marla eGearing Howard D. Rees Howard D. Rees Howard D. Rees Junmin ePeng Junmin ePeng Junmin ePeng Junmin ePeng James J. Lah James J. Lah James J. Lah Allan I. Levey Allan I. Levey Allan I. Levey |
| author_facet | Yair M. Gozal Yair M. Gozal Yair M. Gozal Eric B. Dammer Eric B. Dammer Eric B. Dammer Duc M. Duong Duc M. Duong Duc M. Duong Dongmei eCheng Dongmei eCheng Dongmei eCheng Marla eGearing Marla eGearing Marla eGearing Howard D. Rees Howard D. Rees Howard D. Rees Junmin ePeng Junmin ePeng Junmin ePeng Junmin ePeng James J. Lah James J. Lah James J. Lah Allan I. Levey Allan I. Levey Allan I. Levey |
| author_sort | Yair M. Gozal |
| collection | DOAJ |
| description | Frontotemporal lobar degeneration (FTLD) is the most common cause of dementia with pre-senile onset, accounting for as many as 20% of cases. A common subset of FTLD cases is characterized by the presence of ubiquitinated inclusions in vulnerable neurons (FTLD-U). While the pathophysiological mechanisms underlying neurodegeneration in FTLD-U have not yet been elucidated, the presence of inclusions in this disease indicates enhanced aggregation of one or several proteins. Moreover, these inclusions suggest altered expression, processing, or degradation of proteins during FTLD-U pathogenesis. Thus, one approach to understanding disease mechanisms is to delineate the molecular changes in protein composition in FTLD-U brain. Using a combined approach consisting of laser capture microdissection (LCM) and high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 1252 proteins in hippocampal dentate granule cells excised from three post-mortem FTLD-U and three unaffected control cases processed in parallel. Additionally, we employed a labeling-free quantification technique to compare the abundance of the identified proteins between FTLD-U and control cases. Quantification revealed 54 proteins with selective enrichment in FTLD-U, including TAR DNA binding protein 43 (TDP-43), a recently identified component of ubiquitinated inclusions. Moreover, 19 proteins were selectively decreased in FTLD-U. Subsequent immunohistochemical analysis of TDP-43 and three additional protein candidates suggests that our proteomic profiling of FTLD-U dentate granule cells reveals both inclusion-associated proteins and non-aggregated disease-specific proteins. Application of LCM is a valuable tool in the molecular analysis of complex tissues, and its application in the proteomic characterization of neurodegenerative disorders such as FTLD-U may be used to identify proteins altered in disease. |
| first_indexed | 2024-12-22T17:36:58Z |
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| id | doaj.art-aa3cb8bbbbc44d96909f52e757e0ba20 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-22T17:36:58Z |
| publishDate | 2011-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-aa3cb8bbbbc44d96909f52e757e0ba202022-12-21T18:18:30ZengFrontiers Media S.A.Frontiers in Neurology1664-22952011-04-01210.3389/fneur.2011.000247534Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology.Yair M. Gozal0Yair M. Gozal1Yair M. Gozal2Eric B. Dammer3Eric B. Dammer4Eric B. Dammer5Duc M. Duong6Duc M. Duong7Duc M. Duong8Dongmei eCheng9Dongmei eCheng10Dongmei eCheng11Marla eGearing12Marla eGearing13Marla eGearing14Howard D. Rees15Howard D. Rees16Howard D. Rees17Junmin ePeng18Junmin ePeng19Junmin ePeng20Junmin ePeng21James J. Lah22James J. Lah23James J. Lah24Allan I. Levey25Allan I. Levey26Allan I. Levey27Emory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineFrontotemporal lobar degeneration (FTLD) is the most common cause of dementia with pre-senile onset, accounting for as many as 20% of cases. A common subset of FTLD cases is characterized by the presence of ubiquitinated inclusions in vulnerable neurons (FTLD-U). While the pathophysiological mechanisms underlying neurodegeneration in FTLD-U have not yet been elucidated, the presence of inclusions in this disease indicates enhanced aggregation of one or several proteins. Moreover, these inclusions suggest altered expression, processing, or degradation of proteins during FTLD-U pathogenesis. Thus, one approach to understanding disease mechanisms is to delineate the molecular changes in protein composition in FTLD-U brain. Using a combined approach consisting of laser capture microdissection (LCM) and high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 1252 proteins in hippocampal dentate granule cells excised from three post-mortem FTLD-U and three unaffected control cases processed in parallel. Additionally, we employed a labeling-free quantification technique to compare the abundance of the identified proteins between FTLD-U and control cases. Quantification revealed 54 proteins with selective enrichment in FTLD-U, including TAR DNA binding protein 43 (TDP-43), a recently identified component of ubiquitinated inclusions. Moreover, 19 proteins were selectively decreased in FTLD-U. Subsequent immunohistochemical analysis of TDP-43 and three additional protein candidates suggests that our proteomic profiling of FTLD-U dentate granule cells reveals both inclusion-associated proteins and non-aggregated disease-specific proteins. Application of LCM is a valuable tool in the molecular analysis of complex tissues, and its application in the proteomic characterization of neurodegenerative disorders such as FTLD-U may be used to identify proteins altered in disease.http://journal.frontiersin.org/Journal/10.3389/fneur.2011.00024/fullDementiaLaser Capture MicrodissectionMass SpectrometryUbiquitinneurodegeneration |
| spellingShingle | Yair M. Gozal Yair M. Gozal Yair M. Gozal Eric B. Dammer Eric B. Dammer Eric B. Dammer Duc M. Duong Duc M. Duong Duc M. Duong Dongmei eCheng Dongmei eCheng Dongmei eCheng Marla eGearing Marla eGearing Marla eGearing Howard D. Rees Howard D. Rees Howard D. Rees Junmin ePeng Junmin ePeng Junmin ePeng Junmin ePeng James J. Lah James J. Lah James J. Lah Allan I. Levey Allan I. Levey Allan I. Levey Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. Frontiers in Neurology Dementia Laser Capture Microdissection Mass Spectrometry Ubiquitin neurodegeneration |
| title | Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. |
| title_full | Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. |
| title_fullStr | Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. |
| title_full_unstemmed | Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. |
| title_short | Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: Application of laser capture technology. |
| title_sort | proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration application of laser capture technology |
| topic | Dementia Laser Capture Microdissection Mass Spectrometry Ubiquitin neurodegeneration |
| url | http://journal.frontiersin.org/Journal/10.3389/fneur.2011.00024/full |
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