The essential and downstream common proteins of amyotrophic lateral sclerosis

A protein-protein interaction network analysis

Yimin Mao, Su Wei Kuo, Le Chen, Cj Heckman, Mingchen Jiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.

Original languageEnglish (US)
Article numbere0172246
JournalPloS one
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Protein Interaction Maps
Amyotrophic Lateral Sclerosis
protein-protein interactions
Electric network analysis
Proteins
proteins
dementia
Motor Neurons
motor neurons
Ubiquitin C
Neurodegenerative diseases
Defects
genetic disorders
amyotrophic lateral sclerosis
Biological Phenomena
Frontotemporal Dementia
Genes
Protein C
Neurodegenerative Diseases
Computer Simulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis",
abstract = "Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.",
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The essential and downstream common proteins of amyotrophic lateral sclerosis : A protein-protein interaction network analysis. / Mao, Yimin; Kuo, Su Wei; Chen, Le; Heckman, Cj; Jiang, Mingchen.

In: PloS one, Vol. 12, No. 3, e0172246, 01.03.2017.

Research output: Contribution to journalArticle

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