Alzheimer’s disease is the most common form of dementia, and its prevalence increases exponentially with age. The patients affected gradually lose cognitive function, control over their sense of orientation, their emotions, and other aspects of behavior. Thirty-five million people are now considered to be affected by AD and this number is expected to double in the next few decades. We utilized an AD cell model system for a proteomic study by using mass spectrometry. To mimic early events in AD, LAN5 neuroblastoma cell were incubated for a short time with a recombinant form of A?42 (rA?42), a peptide involved in AD, and the extracted proteins were utilized for the proteome analysis. Furthermore, we used bioinformatics tools to identify networks, associated processes, pathways, etc. The potential modulation of pathways suggested by the similarity of GO terms and presence of protein-protein interaction networks among significantly modulated proteins was explored using the bioinformatic tool KEGG. Pathway enrichment analysis was conducted for up and down regulated protein groups, and four pathways were identified. In particular, the Spliceosome pathway identified in the under-expressed protein group was reported by KEGG to be the most significantly enriched. To confirm the effect of A?42 on the spliceosomal pathway, the level of expression of SmB/B’/N (a component of the spliceosomal machinery) was measured. However, further studies are necessary to fully elucidate the the down-regulation effect of the spliceosome proteins in AD, and how this may contribute to the early event in this disorder.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Alzheimer’s disease ; Aβ42 ; splicing ; AD early events ; orbitrap ; Human
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Principal Investigators: (in alphabetical order) |
Marta Di Carlo, Istituto di Biomedicina ed Immunologia Molecolare (IBIM) CNR, Via U. La Malfa 153, Palermo 90146, Italy, N/A |
| Submitting User: | ccms |
Nuzzo D, Inguglia L, Walters J, Picone P, Di Carlo M.
A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease A? Peptide: Spliceosome Impairment.
J. Proteome Res. 2017 Apr 7;16(4):1526-1541. Epub 2017 Mar 6.
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