C9ORF72 Repeat Expansion Affects the Proteome of Primary Skin Fibroblasts in ALS.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34638725", "kind": "science-record", "revision": 4, "content_hash": "sha256:5095011fb791e3c40ccd512db061d30d737391360ec752a1348b635e301595e6", "created_at": "2026-11-01T17:36:17Z", "updated_at": "2026-11-01T22:04:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "C9ORF72 Repeat Expansion Affects the Proteome of Primary Skin Fibroblasts in ALS.", "doi": "10.3390/ijms221910385", "pmid": "34638725", "authors": ["Marta Lualdi", "Adeena Shafique", "Edoardo Pedrini", "Luisa Pieroni", "Viviana Greco", "Massimo Castagnola", "Giorgia Cucina", "Lucia Corrado", "Alice Di Pierro", "Fabiola De Marchi", "Lara Camillo", "Claudia Colombrita", "Marianna D'Anca", "Tiziana Alberio", "Sandra D'Alfonso", "Mauro Fasano"], "journal": "International journal of molecular sciences", "year": 2021, "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of the corticospinal motor neurons, which ultimately leads to death. The repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) represents the most common genetic cause of ALS and it is also involved in the pathogenesis of other neurodegenerative disorders. To offer insights into C9ORF72-mediated pathogenesis, we quantitatively analyzed the proteome of patient-derived primary skin fibroblasts from ALS patients carrying the C9ORF72 mutation compared with ALS patients who tested negative for it. Differentially expressed proteins were identified, used to generate a protein-protein interaction network and subjected to a functional enrichment analysis to unveil altered molecular pathways. ALS patients were also compared with patients affected by frontotemporal dementia carrying the C9ORF72 repeat expansion. As a result, we demonstrated that the molecular pathways mainly altered in fibroblasts (e.g., protein homeostasis) mirror the alterations observed in C9ORF72-mutated neurons. Moreover, we highlighted novel molecular pathways (nuclear and mitochondrial transports, vesicle trafficking, mitochondrial bioenergetics, glucose metabolism, ER-phagosome crosstalk and Slit/Robo signaling pathway) which might be further investigated as C9ORF72-specific pathogenetic mechanisms. Data are available via ProteomeXchange with the identifier PXD023866.", "claims": [{"id": "claim-method", "statement": "Specifically, a sparse partial least squares discriminant analysis (sPLS-DA) was applied, including all proteins quantified in all samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34638725", "locator": "sections[7] \"2.5. 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