Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in


Journal

Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414

Informations de publication

Date de publication:
24 07 2022
Historique:
received: 09 06 2022
revised: 21 07 2022
accepted: 22 07 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 29 7 2022
Statut: epublish

Résumé

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disease characterized by early-onset spasticity in the lower limbs, axonal-demyelinating sensorimotor peripheral neuropathy, and cerebellar ataxia. Our understanding of ARSACS (genetic basis, protein function, and disease mechanisms) remains partial. The integrative use of organelle-based quantitative proteomics and whole-genome analysis proposed in the present study allowed identifying the affected disease-specific pathways, upstream regulators, and biological functions related to ARSACS, which exemplify a rationale for the development of improved early diagnostic strategies and alternative treatment options in this rare condition that currently lacks a cure. Our integrated results strengthen the evidence for disease-specific defects related to bioenergetics and protein quality control systems and reinforce the role of dysregulated cytoskeletal organization in the pathogenesis of ARSACS.

Identifiants

pubmed: 35892334
pii: biom12081024
doi: 10.3390/biom12081024
pmc: PMC9331974
pii:
doi:

Substances chimiques

Heat-Shock Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Federica Morani (F)

Department of Biology, University of Pisa, 56126 Pisa, Italy.

Stefano Doccini (S)

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy.

Daniele Galatolo (D)

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy.

Francesco Pezzini (F)

Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37129 Verona, Italy.

Rabah Soliymani (R)

HiLIFE, Meilahti Clinical Proteomics Core Facility, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland.

Alessandro Simonati (A)

Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37129 Verona, Italy.

Maciej M Lalowski (MM)

HiLIFE, Meilahti Clinical Proteomics Core Facility, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland.
Institute of Bioorganic Chemistry, PAS, Department of Biomedical Proteomics, 61-704 Poznań, Poland.

Federica Gemignani (F)

Department of Biology, University of Pisa, 56126 Pisa, Italy.

Filippo M Santorelli (FM)

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy.

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