MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/x01/MSV000081021/primaryOK2000000Marta Di Carlohttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=391b7092efdd44efb75504f9d2df8b9amarta.dicarlo@ibim.cnr.itMassIVE33MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetProteomicsLTQ Orbitrap VelosHomo Sapiens (ncbitaxon:9606)Istituto di Biomedicina ed Immunologia Molecolare (IBIM) CNR, Via U. La Malfa 153, Palermo 90146, ItalyProteomic 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.A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment.Comments on "Two-mutation models for bone cancer due to radium, strontium and plutonium" by Bijwaard et al. (Radiat. Res. 162, 171-184, 2004).Nuzzo Domenico D, Inguglia Luigi L, Walters Jessica J, Picone Pasquale P, Di Carlo Marta MLloyd Ray D RD, Miller Scott C SC, Taylor Glenn N GN, Bruenger Fred W FW, Jee Webster S S WSAlzheimer Senile Dementia, Presenile Alzheimer Dementia, Senile, Disease, Alzheimer disease, ALZHEIMERS DIS, Alzheimers Diseases, Peptidomics, Alzheimer Syndrome, Acute Confusional Senile Dementia, Early Onset, Sclerosis, familial, Early Onset Alzheimer Disease, Focal Onset, Alzheimer's Dementia, Alzheimer's disease, Peptide, unspecified (disorder), Primary Senile Degenerative Dementia, Concept, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, Alzheimer Dementias, ALZHEIMER DIS, Primary Senile Degenerative, polypeptide, peptide, AD, Polypeptides, unspecified, Role Concept, peptido, [X]Dementia in Alzheimer's disease, Roles, Alzheimer's Diseases, Role, Concepts, NOS, Dementia, LATE ONSET ALZHEIMER DIS, Alzheimers, Familial Alzheimer Disease (FAD), Alzheimer Diseases, peptides, DAT - Dementia Alzheimer's type, Dementia in Alzheimer's disease, Alzheimer, Alzheimer's Disease Pathway, Dementias, Alzheimer Type Senile Dementia, Alzheimer-Type (ATD), Focal Onset Alzheimer's Disease, Late Onset Alzheimer Disease, Alzheimer Dementia, Alzheimer Sclerosis, FOCAL ONSET ALZHEIMERS DIS, Presenile Dementia, spliceosome., Senile Dementia, Late Onset, AD - Alzheimer's disease, Alzheimer Disease, Familial (FAD), Alzheimer Type Dementia, Role Concepts, Acute Confusional, Dementia in Alzheimer's disease (disorder), Alzheimer-Type Dementia (ATD), Spliceosome, Peptid, peptidos, ALZHEIMER DIS EARLY ONSET, Alzheimer's Disease, Alzheimer's disease (disorder), Polypeptide, Presenile, Alzheimers Dementia, Familial Alzheimer Diseases (FAD), spliceosome complex, Alzheimers disease, Alzheimer Type Dementia (ATD), Dementia of the Alzheimer's typeRegret, projections, Forms, Cognitive Function, determination, Period Prevalence, Amentias, protein, sci, Downregulation, prevention, Long Term, dmTAF[[II]]230, peptide, Polypeptides, protein polypeptide chains, Point Prevalence, peptido, diseases, spliceosome, Orientation, Point Prevalences, HOW, How, diseases and disorders, Analysis, dementia (disease), protein aggregate, dementia, Fs(3)Hor, prevention and control, Effect, Paranoid Dementia, Cognitive Orientation, Sm B, l(3)j5D5, Psychological, Mass Spectrum Analysis, 24B, B, human disease, DmelCG2684, reference sample, TFIID TAF250, peptides, CG5352, Analyses, Prevalences, cel, Amentia, stru, Familial, proteins, l(3)S053606, NTef2, Emotion, CG10293, Sm protein B, preventive measures, l(3)j5B5, set, Cognitions, Functions, papilla, Homo sapiens disease, Familial Dementias, associated, spliceosome complex, Long-Term Effects, single-organism behavior, Senile, Prevalence, 0904/17, dTAF[[II]]230, preventive therapy, Psychological Orientations, Process, frequency, lamina, TAF200, Longterm Effect, flanges, Insight, TAFII-250, TAF250/230, Spectrum Analysis, Acceptance Processes, Fs(3)Sz11, Spectroscopy, shortened, Acceptance Process, TAFII250, Progressive dementia, AU018828, SNRNP-B, Receptor Down-Regulation, SZ1, RENBP, Diseases, shelf, Dementia, non-neoplastic., Senile Paranoid Dementia, shelves, Spectrometry, common, Dementias, CG17603, surveillance, TAF[[II]], projection, morbidity, ridge, DmelCG5352, early, AGE, l(2)SH0509, disease, Patient, Taf250, SR3-5, Horka, CG2684, Fs(3)Horka, Spliceosome, NBL cell, snRNP B, anon-EST:Liang-2.39, Polypeptide, progressive, short, Proteomes, TAF230, Gruppe, small nuclear ribonucleoprotein associated protein B, Mental, other disease, d230, snRNP-B, SmB, Effects, Processes, lamellae, P62, snRPB, number, Gene, dTAFII250, Period Prevalences, Spectrum Analyses, Mental Orientation, protein-containing complex, EfW1, presence, process of organ, lamella, polypeptide chain, AL024368, SMB, dmTAF1, Taf230, Mass, Gene Products, disease or disorder, Orientations, DmF2, Senile Paranoid Dementias, Mass Spectroscopy, TAF250, lod, study, F9F13.90, Taf200, anatomical systems, dTAF[[II]]250, l(3)s2612, smb, occurrence, Longterm, cell, prevalence, F9F13_90, Feeling, stubby, Taf1p, ridges, Long-Term, non-neoplastic, Cognitive Functions, dTAF250, grupos, Clients, DmelCG10293, disorder, Feelings, peptidos, Long-Term Effect, Behaviors, TAF, laminae, incidence, Controlled, Controlling, TAF[[II]]250, grupo, Sm-B, RnBP, protein complex, clone 2.39, Proteins, disorders, GlcNAc 2-epimerase, total expressed protein, l(3)84Ab, medical condition, BG:DS00004.13, qkr, l(3)S090417, Client, Cell, Peptide, Down Regulation, Regrets, group, cognitive function, dTAF230, polypeptide, Insights, count in organism, N-acetyl-D-glucosamine 2-epimerase, MS, Down-Regulation, native protein, Period, natural protein, SM-B, Cognitive Orientations, p230, Down-Regulation (Physiology), KH93F, Long Term Effects, Protein, chemical analysis, TAF[[II]]250/230, condition, TFIID, Mental Orientations, outbreaks, Mass Spectrum Analyses, flange, organ process, SYM10, who, Taf[[II]]250, Acceptance, Mass Spectrum, TAF[[II]]230, Paranoid Dementias, ensemble, prophylaxis, Function, Rest, TAF[II]250, Who/How, Cognitive, Lds, SM11, endemics, Longterm Effects, Protein Gene Products, Familial Dementia, Gene Proteins, processes, DmelCG17603, Senile Paranoid, Psychological Orientation, control, Point, l(2)SH2 0509, cardinality, renin-binding protein, qkr[93F], epidemics, Peptid, assay, Receptor, groupe, TAF1projections, Forms, HNRPDL, Presenile Alzheimer Dementia, dlmo, ALZHEIMERS DIS, determination, DLMO, Early Onset, Rho A, Heterogeneous Nuclear Ribonucleoprotein, positive regulation by symbiont of host non-apoptotic programmed cell death, Neurologic Diseases, Neurologic Degenerative Condition, Early Onset Alzheimer Disease, Downregulation, Alzheimer's disease, Long Term, hdp-a, Neurodegenerative Diseases, SUB, Primary Senile Degenerative, dmTAF[[II]]230, AD, Membrane Tissues, dLmo, dLMO, unspecified, DmelCG1004, Neurologic Disorders, DmelCG12298, rho-1, spliceosome, symptoms, pathogenesis, SCRAMBLED, DRho, cytopathology, AAF01186, Fs(3)Hor, Effect, KIF20A, 8416, Nervous System Degenerative Diseases, Dmrho, LATE ONSET ALZHEIMER DIS, DmelCG2684, Degenerative Condition, Familial Alzheimer Disease (FAD), Alzheimer Diseases, TFIID TAF250, stimulation by symbiont of host programmed cell death, DAT - Dementia Alzheimer's type, cel, C1, C2, membrane region, Tissue, DMRHO, Age of onset, Focal Onset Alzheimer's Disease, NTef2, Neurodegenerative Disorder, Late Onset Alzheimer Disease, neuroblastoma (morphologic abnormality), free, rhoA, RHO1, Rho1, [M]Neuroblastoma NOS (morphologic abnormality), DmelCG8416, Bd, Degenerative Neurologic Disease, AD - Alzheimer's disease, Dlmo, papilla, Alzheimer Type Dementia, rho1, Pathologies, Neurologic Degenerative Disease, Heterogeneous, ALZHEIMER DIS EARLY ONSET, stage, NB - Neuroblastoma, fliH, Presenile, Ftp-3, spliceosome complex, Long-Term Effects, Alzheimers disease, Membrane Tissue, screening, Senile, Neuroblastoma (Schwannian Stroma-Poor), Alzheimer disease, dTAF[[II]]230, Hnrpa2b1, anatomical protrusion, DmRHO-A, Rho-1, Acute Confusional Senile Dementia, Hnrph2, RHOb, familial, STRUBBELIG, lamina, TAF200, Longterm Effect, HSC0013, CG1004, integral to membrane, flanges, Heterogeneous Nuclear, Heterogeneous-Nuclear, TAFII-250, membranous organ component, TAF250/230, Alzheimer's Dementia, Sympathicoblastoma, results, Dm Rho1, Fs(3)Sz11, Alzheimer Type, rhom, shortened, TAFII250, RhoN19, Receptor Down-Regulation, RhoA, Particles, ve, shelf, modulation by symbiont of host system process, RHOM, RhoM, NOS, RHOHP1, Nuclear Ribonucleoprotein, Dementia, Ptd, heterogeneous nuclear ribonucleoprotein complex, Alzheimers, membrane of organ, histopathology, Neuroblastomas, Degenerative Diseases, D-Rho1, AI326383, Alzheimer, shelves, Ve, CG8416, signs, Dementias, HNRNP, Neurologic Disease, RHO, Rho, Alzheimer-Type (ATD), CG17603, TAF[[II]], projection, ridge, DMRHOa, early, DMRHOb, H', HNRPC, Senile Dementia, Taf250, rhomboid/veinlet, Degenerative, hnRNP Particles, spine, Horka, SR3-5, label, Complexes, activation by symbiont of host programmed cell death, Acute Confusional, Lmo, LMO, Alzheimer-Type Dementia (ATD), CG2684, Fs(3)Horka, Spliceosome, ARHD, Alzheimer's Disease, hdp, JKTBP, rho, short, TAF230, Alzheimer Type Dementia (ATD), Dementia of the Alzheimer's type, AT1G11140, Dmelrho, heterogeneous nuclear ribonucleoprotein, d230, nuclear mRNA cis splicing, neuroblastoma, Alzheimers Diseases, DRORHO, Effects, Peptidomics, lamellae, Sclerosis, regulation by symbiont of host system process, Central neuroblastoma, developmental stage, Ftp3, Arhd, Degenerative Neurologic Disorders, Gene, dTAFII250, laAUF1, Focal Onset, EfW1, process of organ, cerebral degeneration disease, Rho GTPase, unspecified (disorder), CG12298, JKTBP2, protrusion, ALZHEIMER DIS, lamella, hnRNP, Ribonucleoproteins, [X]Dementia in Alzheimer's disease, DRhoA, dmTAF1, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Taf230, dttg, integral component of membrane, Gene Products, causality., DmF2, CG6500, Informatin, SNRPC, TAF250, lod, Ribonucleoprotein, Nervous System, Taf200, dRhoA, anatomical systems, dTAF[[II]]250, beadex/dLMO, Longterm, cell, Tissues, mei-1794, stubby, Taf1p, ridges, causes, Long-Term, DRho1, Neurodegenerative Disorders, FOCAL ONSET ALZHEIMERS DIS, DrhoA, Presenile Dementia, OPN2, dTAF250, Neurologic, via U2-type spliceosome, Neurologic Degenerative Diseases, RhoHP1, Alzheimer Disease, [M]Neuroblastoma NOS, Informofer, hnRNP Complexes, Degenerative Neurologic Diseases, Drho1, region of membrane, Spinal Cord, Long-Term Effect, SRF9, dRho1, Alzheimer's disease (disorder), TAF, Alzheimers Dementia, laminae, DmelCG6500, Alzheimer Senile Dementia, membrane, Disease, Rho kinase, TAF[[II]]250, Neurologic Disorder, findings, activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, Alzheimer Syndrome, l(2)52Fa, Proteins, iks, l(3)84Ab, BG:DS00004.13, l(2)k02107b, Cell, Down Regulation, Primary Senile Degenerative Dementia, dTAF230, Degenerative Neurologic Disorder, [X]Dementia in Alzheimer's disease (disorder), STRUBBELIG-RECEPTOR FAMILY 9, Alzheimer Dementias, Down-Regulation, p230, Down-Regulation (Physiology), Alzheimer's Diseases, Long Term Effects, Protein, chemical analysis, whole membrane, TAF[[II]]250/230, TFIID, NB, LGMD1G, dnRho, flange, organ process, Taf[[II]]250, Degenerative Conditions, transmembrane, TAF[[II]]230, Neuroblastoma, Dementia in Alzheimer's disease, Dub, Alzheimer's Disease Pathway, Alzheimer Type Senile Dementia, E3.10/J3.8, Neurologic Degenerative Conditions, TAF[II]250, Age symptoms begin, Membrane, Lds, Alzheimer Dementia, Longterm Effects, Alzheimer Sclerosis, neuroblastoma NOS (morphologic abnormality), hnRNP Proteins, Protein Gene Products, hld, Gene Proteins, processes, DmelCG17603, Late Onset, (Neuroblastoma NOS) or (sympathicoblastoma), Familial (FAD), Dementia in Alzheimer's disease (disorder), Neurodegenerative Disease, Central Nervous System, assay, Hnrpa2, Receptor, DXHXS1271E, biopsy, Familial Alzheimer Diseases (FAD), T19D16.8, n(2)k07236, SCM, Heterogeneous Nuclear Ribonucleoproteins, TAF1Mass Spectrum Analysis, Mass Spectrum, other disease, human disease, peptides, Analyses, disorders, Spectrometry, medical condition, Spectrum Analyses, Spectrum Analysis, Peptide, Concept, non-neoplastic, Spectroscopy, polypeptide, peptide, spliceosome., disease, Polypeptides, MS, Role Concept, peptido, diseases, Roles, Role Concepts, Diseases, Mass, Role, Concepts, disease or disorder, Spliceosome, condition, disorder, diseases and disorders, Homo sapiens disease, Peptid, peptidos, Polypeptide, Analysis, spliceosome complex, Mass Spectrum Analyses, Mass Spectroscopy0PXD002842trueA Mass Spectrometry Approach Reveals a New Toxic Role For Alzheimer’s Disease A? Peptide: SPLICEOSOME IMPAIRMENTAlzheimer’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.Thu Apr 27 11:12:00 BST 2017MSV00008102128157316