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Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model

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...

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Autores principales: Morani, Federica, Doccini, Stefano, Galatolo, Daniele, Pezzini, Francesco, Soliymani, Rabah, Simonati, Alessandro, Lalowski, Maciej M., Gemignani, Federica, Santorelli, Filippo M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331974/
https://www.ncbi.nlm.nih.gov/pubmed/35892334
http://dx.doi.org/10.3390/biom12081024
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author Morani, Federica
Doccini, Stefano
Galatolo, Daniele
Pezzini, Francesco
Soliymani, Rabah
Simonati, Alessandro
Lalowski, Maciej M.
Gemignani, Federica
Santorelli, Filippo M.
author_facet Morani, Federica
Doccini, Stefano
Galatolo, Daniele
Pezzini, Francesco
Soliymani, Rabah
Simonati, Alessandro
Lalowski, Maciej M.
Gemignani, Federica
Santorelli, Filippo M.
author_sort Morani, Federica
collection PubMed
description 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.
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spelling pubmed-93319742022-07-29 Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model Morani, Federica Doccini, Stefano Galatolo, Daniele Pezzini, Francesco Soliymani, Rabah Simonati, Alessandro Lalowski, Maciej M. Gemignani, Federica Santorelli, Filippo M. Biomolecules Article 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. MDPI 2022-07-24 /pmc/articles/PMC9331974/ /pubmed/35892334 http://dx.doi.org/10.3390/biom12081024 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morani, Federica
Doccini, Stefano
Galatolo, Daniele
Pezzini, Francesco
Soliymani, Rabah
Simonati, Alessandro
Lalowski, Maciej M.
Gemignani, Federica
Santorelli, Filippo M.
Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title_full Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title_fullStr Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title_full_unstemmed Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title_short Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations in SACS KO Cell Model
title_sort integrative organelle-based functional proteomics: in silico prediction of impaired functional annotations in sacs ko cell model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331974/
https://www.ncbi.nlm.nih.gov/pubmed/35892334
http://dx.doi.org/10.3390/biom12081024
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