Cargando…

Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formati...

Descripción completa

Detalles Bibliográficos
Autores principales: Capucciati, Andrea, Zucca, Fabio A., Monzani, Enrico, Zecca, Luigi, Casella, Luigi, Hofer, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224073/
https://www.ncbi.nlm.nih.gov/pubmed/34064062
http://dx.doi.org/10.3390/antiox10060824
_version_ 1783711818583113728
author Capucciati, Andrea
Zucca, Fabio A.
Monzani, Enrico
Zecca, Luigi
Casella, Luigi
Hofer, Tim
author_facet Capucciati, Andrea
Zucca, Fabio A.
Monzani, Enrico
Zecca, Luigi
Casella, Luigi
Hofer, Tim
author_sort Capucciati, Andrea
collection PubMed
description Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube.
format Online
Article
Text
id pubmed-8224073
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-82240732021-06-25 Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models Capucciati, Andrea Zucca, Fabio A. Monzani, Enrico Zecca, Luigi Casella, Luigi Hofer, Tim Antioxidants (Basel) Review Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube. MDPI 2021-05-21 /pmc/articles/PMC8224073/ /pubmed/34064062 http://dx.doi.org/10.3390/antiox10060824 Text en © 2021 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 Review
Capucciati, Andrea
Zucca, Fabio A.
Monzani, Enrico
Zecca, Luigi
Casella, Luigi
Hofer, Tim
Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title_full Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title_fullStr Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title_full_unstemmed Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title_short Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
title_sort interaction of neuromelanin with xenobiotics and consequences for neurodegeneration; promising experimental models
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224073/
https://www.ncbi.nlm.nih.gov/pubmed/34064062
http://dx.doi.org/10.3390/antiox10060824
work_keys_str_mv AT capucciatiandrea interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels
AT zuccafabioa interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels
AT monzanienrico interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels
AT zeccaluigi interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels
AT casellaluigi interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels
AT hofertim interactionofneuromelaninwithxenobioticsandconsequencesforneurodegenerationpromisingexperimentalmodels