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A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment
- Source :
- Journal of proteome research. 16(4)
- Publication Year :
- 2017
-
Abstract
- Proteomic changes have been described in many neurodegenerative diseases, including Alzheimer's disease (AD). However, the early events in the onset of the pathology are yet to be fully elucidated. A cell model system in which LAN5 neuroblastoma cells were incubated for a short time with a recombinant form of Aβ42 was utilized. Proteins extracted from these cells were subjected to shotgun proteomics analysis by LTQ-Orbitrap-MS followed by label-free quantitation. By bioinformatics tools we found that the most significant of those found to be up-regulated were related to cytoskeletal dynamics (Rho related) and membrane-related processes. The most significant of the down-regulated proteins were hnRNP-related. In particular, hnRNPs involved in ribosomal biogenesis and in splicing were down-regulated. The latter of these processes stood out as it was highlighted ubiquitously and with the highest significance in the results of every analysis. Furthermore, our findings revealed down-regulation at every stage of the splicing process through down-regulation of every subunit of the spliceosome. Dysregulation of the spliceosome was also confirmed using a Western blot. In conclusion, these data suggest dysregulation of the proteins and processes identified as early events in pathogenesis of AD following Aβ accumulation.
- Subjects :
- 0301 basic medicine
Spliceosome
Amyloid beta-Peptide
Proteome
Computational biology
Disease
Biology
Biochemistry
law.invention
early events in AD
03 medical and health sciences
Neuroblastoma
0302 clinical medicine
law
Alzheimer Disease
Cell Line, Tumor
Humans
Shotgun proteomics
Cytoskeleton
Genetics
Amyloid beta-Peptides
Chemistry (all)
Cell Membrane
General Chemistry
Ribosomal RNA
Alzheimer's disease
Recombinant Protein
shotgun proteomic
Recombinant Proteins
030104 developmental biology
Gene Expression Regulation
RNA splicing
Recombinant DNA
Spliceosomes
030217 neurology & neurosurgery
Biogenesis
Human
Subjects
Details
- ISSN :
- 15353907
- Volume :
- 16
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of proteome research
- Accession number :
- edsair.doi.dedup.....c8eea27cc8c76a47f9e68732906c8132