Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions

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ID: 114189
2007
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Abstract
Neurodegenerative disorders share a process of aggregation of insoluble protein. Frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) is characterized by the presence of ubiquitin and TDP-43 positive aggregates which are likely related to specific gene expression profiles. We carried out gene expression microarray analysis on post-mortem brain tissue from FTLD-U, FTLD-MND, and controls. Using total RNA from carefully dissected frontal cortical layer II, we obtained gene expression profiles showing that FTLD-U and controls differ in over 100 networks, including those involved in synapse formation, the ubiquitin-proteasome system, endosomal sorting, and apoptosis. We performed qRT-PCR validation for three genes, representative of three different networks. Dynein axonemal light intermediate chain 1 (DNALI1) (microtubule/cytoskeleton network associated) expression was 3-fold higher and myeloid differentiation primary response gene 88 (MYD88) (signal transduction network) was 3.3 times higher in FTLD-U than FTLD-MND and controls; annexin A2 (ANXA2) (endosomal sorting) expression was 11.3-fold higher in FTLD-U than FTLD-MND and 2.3-fold higher than controls. The identification of progranulin (PGRN) gene mutations and TDP-43 as the major protein component of the ubiquitinated inclusions, are two recent landmark discoveries in the field of FTLD-U. We found 1.5-fold increase in TDP-43 in both FTLD-MND and FTLD-U while progranulin showed no gene expression differences between controls and FTLD-MND. However, one of the FTLD-U cases tested by Affymetrix microarray showed “absence call” of this transcript, suggesting absent or decreased gene expression. Our findings point to specific gene-linked-pathways which may be influenced by neurodegenerative disease process and may be targeted for further exploration.
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mishra2007actagene Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Manjari Mishra;Tatjana Paunesku;Gayle E. Woloschak;Teepu Siddique;Lihua (Julie) Zhu;Simon Lin;Kristin Greco;Eileen H. Bigio;Manjari Mishra;Tatjana Paunesku;Gayle E. Woloschak;Teepu Siddique;Lihua (Julie) Zhu;Simon Lin;Kristin Greco;Eileen H. Bigio;
Journal acta neuropathologica
Year 2007
DOI
doi:10.1007/s00401-007-0240-7
URL
https://link.springer.com/article/10.1007/s00401-007-0240-7
Keywords
pathology neurosciences

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