Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zanardi, Alan, Alessio, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783640832803340288
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
work_keys_str_mv AT zanardialan ceruloplasmindeamidationinneurodegenerationfromlosstogainoffunction
AT alessiomassimo ceruloplasmindeamidationinneurodegenerationfromlosstogainoffunction