A bioinformatics analysis ofMass Spectrometry approach reveals a new target of A ?42 peptide

Proteomic changes have been described in different neurodegenerative disease including Alzheimer's disease (AD). This pathology 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. AD cell model system in which LAN5 neuroblastoma cell were incubated for short time with a recombinant form of A?42 (rA?42), a peptide involved in AD, was utilized for a study of the proteome by mass spectrometry. Furthermore, we used bioinformatics tools to mine databases and present relatedness in the form of 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. 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. Proteins were extracted from LAN5 cells treated with rA?42 at differing concentrations and times, and a Western blot was performed. SmB/B'/N levels were found to decrease in a time and dose dependent manner relative to the control suggesting that impaired splicing can occur. 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.