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Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS
Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655709/ https://www.ncbi.nlm.nih.gov/pubmed/36361774 http://dx.doi.org/10.3390/ijms232112985 |
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author | Vourkou, Ergina Paspaliaris, Vassilis Bourouliti, Anna Zerva, Maria-Christina Prifti, Engie Papanikolopoulou, Katerina Skoulakis, Efthimios M. C. |
author_facet | Vourkou, Ergina Paspaliaris, Vassilis Bourouliti, Anna Zerva, Maria-Christina Prifti, Engie Papanikolopoulou, Katerina Skoulakis, Efthimios M. C. |
author_sort | Vourkou, Ergina |
collection | PubMed |
description | Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a representative single isoform. However, the six human tau isoforms present overlapping but distinct distributions in the brain and are differentially involved in particular tauopathies. These observations support the notion that tau isoforms possess distinct functional properties important for both physiology and pathology. To address this hypothesis, the six human brain tau isoforms were expressed singly in the Drosophila brain and their effects in an established battery of assays measuring neuronal dysfunction, vulnerability to oxidative stress and life span were systematically assessed comparatively. The results reveal isoform-specific effects clearly not attributed to differences in expression levels but correlated with the number of microtubule-binding repeats and the accumulation of a particular isoform in support of the functional differentiation of these tau isoforms. Delineation of isoform-specific effects is essential to understand the apparent differential involvement of each tau isoform in tauopathies and their contribution to neuronal dysfunction and toxicity. |
format | Online Article Text |
id | pubmed-9655709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96557092022-11-15 Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS Vourkou, Ergina Paspaliaris, Vassilis Bourouliti, Anna Zerva, Maria-Christina Prifti, Engie Papanikolopoulou, Katerina Skoulakis, Efthimios M. C. Int J Mol Sci Article Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a representative single isoform. However, the six human tau isoforms present overlapping but distinct distributions in the brain and are differentially involved in particular tauopathies. These observations support the notion that tau isoforms possess distinct functional properties important for both physiology and pathology. To address this hypothesis, the six human brain tau isoforms were expressed singly in the Drosophila brain and their effects in an established battery of assays measuring neuronal dysfunction, vulnerability to oxidative stress and life span were systematically assessed comparatively. The results reveal isoform-specific effects clearly not attributed to differences in expression levels but correlated with the number of microtubule-binding repeats and the accumulation of a particular isoform in support of the functional differentiation of these tau isoforms. Delineation of isoform-specific effects is essential to understand the apparent differential involvement of each tau isoform in tauopathies and their contribution to neuronal dysfunction and toxicity. MDPI 2022-10-26 /pmc/articles/PMC9655709/ /pubmed/36361774 http://dx.doi.org/10.3390/ijms232112985 Text en © 2022 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 | Article Vourkou, Ergina Paspaliaris, Vassilis Bourouliti, Anna Zerva, Maria-Christina Prifti, Engie Papanikolopoulou, Katerina Skoulakis, Efthimios M. C. Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title | Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title_full | Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title_fullStr | Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title_full_unstemmed | Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title_short | Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS |
title_sort | differential effects of human tau isoforms to neuronal dysfunction and toxicity in the drosophila cns |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655709/ https://www.ncbi.nlm.nih.gov/pubmed/36361774 http://dx.doi.org/10.3390/ijms232112985 |
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