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Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function
Neurodegenerative disorders can induce modifications of several proteins; one of which is ceruloplasmin (Cp), a ferroxidase enzyme found modified in the cerebrospinal fluid (CSF) of neurodegenerative diseases patients. Cp modifications are caused by the oxidation induced by the pathological environm...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827708/ https://www.ncbi.nlm.nih.gov/pubmed/33440850 http://dx.doi.org/10.3390/ijms22020663 |
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author | Zanardi, Alan Alessio, Massimo |
author_facet | Zanardi, Alan Alessio, Massimo |
author_sort | Zanardi, Alan |
collection | PubMed |
description | Neurodegenerative disorders can induce modifications of several proteins; one of which is ceruloplasmin (Cp), a ferroxidase enzyme found modified in the cerebrospinal fluid (CSF) of neurodegenerative diseases patients. Cp modifications are caused by the oxidation induced by the pathological environment and are usually associated with activity loss. Together with oxidation, deamidation of Cp was found in the CSF from Alzheimer’s and Parkinson’s disease patients. Protein deamidation is a process characterized by asparagine residues conversion in either aspartate or isoaspartate, depending on protein sequence/structure and cellular environment. Cp deamidation occurs at two Asparagine-Glycine-Arginine (NGR)-motifs which, once deamidated to isoAspartate-Glycine-Arginine (isoDGR), bind integrins, a family of receptors mediating cell adhesion. Therefore, on the one hand, Cp modifications lead to loss of enzymatic activity, while on the other hand, these alterations confer gain of function to Cp. In fact, deamidated Cp binds to integrins and triggers intracellular signaling on choroid plexus epithelial cells, changing cell functioning. Working in concert with the oxidative environment, Cp deamidation could reach different target cells in the brain, altering their physiology and causing detrimental effects, which might contribute to the pathological mechanism. |
format | Online Article Text |
id | pubmed-7827708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78277082021-01-25 Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function Zanardi, Alan Alessio, Massimo Int J Mol Sci Review Neurodegenerative disorders can induce modifications of several proteins; one of which is ceruloplasmin (Cp), a ferroxidase enzyme found modified in the cerebrospinal fluid (CSF) of neurodegenerative diseases patients. Cp modifications are caused by the oxidation induced by the pathological environment and are usually associated with activity loss. Together with oxidation, deamidation of Cp was found in the CSF from Alzheimer’s and Parkinson’s disease patients. Protein deamidation is a process characterized by asparagine residues conversion in either aspartate or isoaspartate, depending on protein sequence/structure and cellular environment. Cp deamidation occurs at two Asparagine-Glycine-Arginine (NGR)-motifs which, once deamidated to isoAspartate-Glycine-Arginine (isoDGR), bind integrins, a family of receptors mediating cell adhesion. Therefore, on the one hand, Cp modifications lead to loss of enzymatic activity, while on the other hand, these alterations confer gain of function to Cp. In fact, deamidated Cp binds to integrins and triggers intracellular signaling on choroid plexus epithelial cells, changing cell functioning. Working in concert with the oxidative environment, Cp deamidation could reach different target cells in the brain, altering their physiology and causing detrimental effects, which might contribute to the pathological mechanism. MDPI 2021-01-11 /pmc/articles/PMC7827708/ /pubmed/33440850 http://dx.doi.org/10.3390/ijms22020663 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Zanardi, Alan Alessio, Massimo Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title | Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title_full | Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title_fullStr | Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title_full_unstemmed | Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title_short | Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function |
title_sort | ceruloplasmin deamidation in neurodegeneration: from loss to gain of function |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827708/ https://www.ncbi.nlm.nih.gov/pubmed/33440850 http://dx.doi.org/10.3390/ijms22020663 |
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