Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions
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 differenc…
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Intersection of the microglia signature gene list with 46 publicly available data sets for differentially regulated genes in neurodegenerative and behavioral disorders revealed significant enrichment or depletion of microglia signature genes in 28 of the 46 data sets.
“We then intersected this gene list with 46 publicly available data sets for differentially regulated genes in neurodegenerative and behavioral disorders derived from microarray or RNA-seq analysis of intact tissue (39–53). Two-sided Fisher’s exact tests revealed significant enrichment or depletion of microglia signature genes in 28 of the 46 data sets (Table S3).”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [45]
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- Authors
- Mishra, M., Paunesku, T., Woloschak, G. E., Siddique, T., Zhu, L., Lin, S., Greco, K., & Bigio, E. H.
- Venue
- Acta Neuropathologica
- Published
- 2007-06-14
- Volume
- 114
- Issue
- 1
- Pages
- 81-94
- ISSN
- 0001-6322
- 1432-0533
- Cited by
- 84
- References
- 2
- Language
- en
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