A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment

Luigi Inguglia, Domenico Nuzzo, Pasquale Picone, Luigi Inguglia, Jessica Walters, Marta Di Carlo, Domenico Nuzzo, Marta Di Carlo

Risultato della ricerca: Article

8 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1526-1541
Numero di pagine16
RivistaJournal of Proteome Research
Volume16
Stato di pubblicazionePublished - 2017

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Spliceosomes
Poisons
Firearms
Proteomics
Alzheimer Disease
Peptides
Down-Regulation
Heterogeneous-Nuclear Ribonucleoproteins
Neurodegenerative diseases
Proteins
Pathology
Bioinformatics
Computational Biology
Neuroblastoma
Neurodegenerative Diseases
Labels
Western Blotting
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Chemistry(all)

Cita questo

Inguglia, L., Nuzzo, D., Picone, P., Inguglia, L., Walters, J., Di Carlo, M., ... Di Carlo, M. (2017). A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment. Journal of Proteome Research, 16, 1526-1541.

A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment. / Inguglia, Luigi; Nuzzo, Domenico; Picone, Pasquale; Inguglia, Luigi; Walters, Jessica; Di Carlo, Marta; Nuzzo, Domenico; Di Carlo, Marta.

In: Journal of Proteome Research, Vol. 16, 2017, pag. 1526-1541.

Risultato della ricerca: Article

Inguglia, L, Nuzzo, D, Picone, P, Inguglia, L, Walters, J, Di Carlo, M, Nuzzo, D & Di Carlo, M 2017, 'A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment', Journal of Proteome Research, vol. 16, pagg. 1526-1541.
Inguglia, Luigi ; Nuzzo, Domenico ; Picone, Pasquale ; Inguglia, Luigi ; Walters, Jessica ; Di Carlo, Marta ; Nuzzo, Domenico ; Di Carlo, Marta. / A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment. In: Journal of Proteome Research. 2017 ; Vol. 16. pagg. 1526-1541.
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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.",
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AU - Inguglia, Luigi

AU - Nuzzo, Domenico

AU - Picone, Pasquale

AU - Inguglia, Luigi

AU - Walters, Jessica

AU - Di Carlo, Marta

AU - Nuzzo, Domenico

AU - Di Carlo, Marta

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N2 - 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.

AB - 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.

KW - Alzheimer's disease; early events in AD; shotgun proteomics; spliceosome; Alzheimer Disease; Amyloid beta-Peptides; Cell Line

KW - Tumor; Cell Membrane; Cytoskeleton; Gene Expression Regulation; Humans; Neuroblastoma; Proteome; Recombinant Proteins; Spliceosomes; Biochemistry; Chemistry (all)

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