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Ion Channel Formation by Tau Protein: Implications for Alzheimer’s Disease and Tauopathies
[Image: see text] Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion p...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690196/ https://www.ncbi.nlm.nih.gov/pubmed/26575330 http://dx.doi.org/10.1021/acs.biochem.5b00988 |
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author | Patel, Nirav Ramachandran, Srinivasan Azimov, Rustam Kagan, Bruce L. Lal, Ratnesh |
author_facet | Patel, Nirav Ramachandran, Srinivasan Azimov, Rustam Kagan, Bruce L. Lal, Ratnesh |
author_sort | Patel, Nirav |
collection | PubMed |
description | [Image: see text] Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion permeable channels. Our results demonstrate that tau can form such channels, but only under acidic conditions. The channels formed are remarkably similar to amyloid peptide channels in their appearance, physical and electrical size, permanence, lack of ion selectivity, and multiple channel conductances. These channels differ from amyloid channels in their voltage dependence and resistance to blockade by zinc ion. These channels could explain tau’s pathologic role in disease by lowering membrane potential, dysregulating calcium, depolarizing mitochondria, or depleting energy stores. Tau might also combine with amyloid beta peptides to form toxic channels. |
format | Online Article Text |
id | pubmed-4690196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-46901962016-01-05 Ion Channel Formation by Tau Protein: Implications for Alzheimer’s Disease and Tauopathies Patel, Nirav Ramachandran, Srinivasan Azimov, Rustam Kagan, Bruce L. Lal, Ratnesh Biochemistry [Image: see text] Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion permeable channels. Our results demonstrate that tau can form such channels, but only under acidic conditions. The channels formed are remarkably similar to amyloid peptide channels in their appearance, physical and electrical size, permanence, lack of ion selectivity, and multiple channel conductances. These channels differ from amyloid channels in their voltage dependence and resistance to blockade by zinc ion. These channels could explain tau’s pathologic role in disease by lowering membrane potential, dysregulating calcium, depolarizing mitochondria, or depleting energy stores. Tau might also combine with amyloid beta peptides to form toxic channels. American Chemical Society 2015-11-17 2015-12-22 /pmc/articles/PMC4690196/ /pubmed/26575330 http://dx.doi.org/10.1021/acs.biochem.5b00988 Text en Copyright © 2015 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 | Patel, Nirav Ramachandran, Srinivasan Azimov, Rustam Kagan, Bruce L. Lal, Ratnesh Ion Channel Formation by Tau Protein: Implications for Alzheimer’s Disease and Tauopathies |
title | Ion Channel Formation by Tau Protein: Implications
for Alzheimer’s Disease and Tauopathies |
title_full | Ion Channel Formation by Tau Protein: Implications
for Alzheimer’s Disease and Tauopathies |
title_fullStr | Ion Channel Formation by Tau Protein: Implications
for Alzheimer’s Disease and Tauopathies |
title_full_unstemmed | Ion Channel Formation by Tau Protein: Implications
for Alzheimer’s Disease and Tauopathies |
title_short | Ion Channel Formation by Tau Protein: Implications
for Alzheimer’s Disease and Tauopathies |
title_sort | ion channel formation by tau protein: implications
for alzheimer’s disease and tauopathies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690196/ https://www.ncbi.nlm.nih.gov/pubmed/26575330 http://dx.doi.org/10.1021/acs.biochem.5b00988 |
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