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Testing Amyloid Cross-Toxicity in the Vertebrate Brain
[Image: see text] While amyloid proteins such as amyloid β (Aβ),α-synuclein, tau, and lysozyme are known to be prion-like; emerging data have revealed that they are also able to seed the misfolding of prion-like proteins differing in sequence. In the present study, we have developed a tool designed...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331027/ https://www.ncbi.nlm.nih.gov/pubmed/32637834 http://dx.doi.org/10.1021/acsomega.0c01819 |
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author | Henríquez, Gabriela Mendez, Lois Schmid, Ariel N. Guerrero, Erick D. Collins, Stephen A. Castañeda, Edward Narayan, Mahesh |
author_facet | Henríquez, Gabriela Mendez, Lois Schmid, Ariel N. Guerrero, Erick D. Collins, Stephen A. Castañeda, Edward Narayan, Mahesh |
author_sort | Henríquez, Gabriela |
collection | PubMed |
description | [Image: see text] While amyloid proteins such as amyloid β (Aβ),α-synuclein, tau, and lysozyme are known to be prion-like; emerging data have revealed that they are also able to seed the misfolding of prion-like proteins differing in sequence. In the present study, we have developed a tool designed to test neurohistochemical outcomes associated with the entry of an amyloid protein into heterotypic neurons, i.e., neurons that do not express the invading amyloid and, instead, endogenously express amyloids differing in sequence. The stereotaxic introduction of Aβ into the rodent tegmental area of the mid-brain revealed that the foreign amyloid had infiltrated into nigral neurons. Furthermore, Aβ was found colocalized with α-synuclein, an amyloid endogenous to the substantia nigra and differing in sequence relative to Aβ. Disruption of α-synuclein status in the substantia nigra is associated with Parkinson’s disease onset and progress. In addition to the study findings, a significant inroad to future neurodegenerative research was made via the stereotaxic introduction of the foreign amyloid. This technique limits the presence of confounding neurometabolic variables that may be prevalent in transgenic animal models of cross-toxicity and, thereby, better addresses the role of individual neuronal factors in cross-toxicity. Finally, the data from this work may help reconcile the high frequency of clinical comorbidity seen in neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-7331027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-73310272020-07-06 Testing Amyloid Cross-Toxicity in the Vertebrate Brain Henríquez, Gabriela Mendez, Lois Schmid, Ariel N. Guerrero, Erick D. Collins, Stephen A. Castañeda, Edward Narayan, Mahesh ACS Omega [Image: see text] While amyloid proteins such as amyloid β (Aβ),α-synuclein, tau, and lysozyme are known to be prion-like; emerging data have revealed that they are also able to seed the misfolding of prion-like proteins differing in sequence. In the present study, we have developed a tool designed to test neurohistochemical outcomes associated with the entry of an amyloid protein into heterotypic neurons, i.e., neurons that do not express the invading amyloid and, instead, endogenously express amyloids differing in sequence. The stereotaxic introduction of Aβ into the rodent tegmental area of the mid-brain revealed that the foreign amyloid had infiltrated into nigral neurons. Furthermore, Aβ was found colocalized with α-synuclein, an amyloid endogenous to the substantia nigra and differing in sequence relative to Aβ. Disruption of α-synuclein status in the substantia nigra is associated with Parkinson’s disease onset and progress. In addition to the study findings, a significant inroad to future neurodegenerative research was made via the stereotaxic introduction of the foreign amyloid. This technique limits the presence of confounding neurometabolic variables that may be prevalent in transgenic animal models of cross-toxicity and, thereby, better addresses the role of individual neuronal factors in cross-toxicity. Finally, the data from this work may help reconcile the high frequency of clinical comorbidity seen in neurodegenerative diseases. American Chemical Society 2020-06-15 /pmc/articles/PMC7331027/ /pubmed/32637834 http://dx.doi.org/10.1021/acsomega.0c01819 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Henríquez, Gabriela Mendez, Lois Schmid, Ariel N. Guerrero, Erick D. Collins, Stephen A. Castañeda, Edward Narayan, Mahesh Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title | Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title_full | Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title_fullStr | Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title_full_unstemmed | Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title_short | Testing Amyloid Cross-Toxicity in the Vertebrate Brain |
title_sort | testing amyloid cross-toxicity in the vertebrate brain |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331027/ https://www.ncbi.nlm.nih.gov/pubmed/32637834 http://dx.doi.org/10.1021/acsomega.0c01819 |
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