PXD023647-1

PXD023647 is an original dataset announced via ProteomeXchange.

Title	Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS
Description	Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that affects motoneurons. Mutations in superoxide dismutase 1 (SOD1) have been described as a causative genetic factor for ALS. Mice overexpressing ALS-linked mutant SOD1 develop ALS symptoms accompanied by histopathological alterations and protein aggregation. Protein disulfide isomerase family member ERp57 is one of the main up-regulated proteins in tissue of ALS patients and mutant SOD1 mice, whereas point mutations in ERp57 were described as possible risk factors. ERp57 catalyzes disulfide bond formation and isomerization in the endoplasmic reticulum (ER), constituting a central component of protein quality control mechanisms. However, the actual contribution of ERp57 to ALS pathogenesis remains to be defined. Here, we studied the consequences of overexpressing ERp57 in ALS onset and progression of mutant SOD1G93A mice. The double transgenic SOD1G93A/ERp57WT mice presented improved motor performance, in addition to delayed deterioration of electrophysiological activity of affected muscles compared to single transgenic SOD1G93A littermates at early symptomatic stage. The overexpression of ERp57 reduced mutant SOD1 aggregation, but only at disease end-stage. Instead, the neuroprotective effects of ERp57 were correlated with preserved muscle innervation. Importantly, proteomic analysis revealed that the overexpression of ERp57 increases the levels of synaptic proteins in the spinal cord. Taken together, our results suggest that ERp57 operates as a disease modifier at early stages by maintaining motoneuron connectivity.
HostingRepository	PRIDE
AnnounceDate	2021-02-08
AnnouncementXML	Submission_2021-02-07_23:08:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Madison Wright
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-18 00:08:06	ID requested
⏵ 1	2021-02-07 23:08:59	announced

Rozas P, Pinto C, Mart, í, nez Traub F, D, í, az R, P, é, rez V, Becerra D, Ojeda P, Ojeda J, Wright MT, Mella J, Plate L, Henr, í, quez JP, Hetz C, Medinas DB, Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS. Acta Neuropathol Commun, 9(1):21(2021) [pubmed]

submitter keyword: amyotrophic lateral sclerosis, mutant SOD1, ERp57, protein aggregation, neuromuscular junction

Claudio Hetz & Danilo B. Medinas
contact affiliation	Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile Center for Geroscience, Brain Health and Metabolism, Santiago, Chile Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile Buck Institute for Research on Aging, Novato, CA, USA
contact email	chetz@med.uchile.cl
lab head
Madison Wright
contact affiliation	Vanderbilt University Department of Chemistry
contact email	madison.t.wright@vanderbilt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023647
     1. Label: PRIDE project
     2. Name: Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS