A Mass Spectrometry Approach Reveals a New Toxic Role For Alzheimer’s Disease Aβ Peptide: SPLICEOSOME IMPAIRMENT

ABSTRACT: 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 Aβ42 (rAβ42), 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 Aβ42 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Alzheimer's Disease

SUBMITTER: Domenico Nuzzo  

LAB HEAD: Marta Di Carlo

PROVIDER: PXD002842 | Pride | 2017-02-06

REPOSITORIES: Pride