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Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools
Alzheimer’s disease (AD) is the most prevalent neurodegenerative dementia in older adults worldwide. Sadly, there are no disease-modifying therapies available for treatment due to the multifactorial complexity of the disease. AD is pathologically characterized by extracellular deposition of amyloid...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150963/ https://www.ncbi.nlm.nih.gov/pubmed/37139514 http://dx.doi.org/10.3389/fnins.2023.1184080 |
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author | Varte, Vanlalrinchhani Munkelwitz, Jeremy W. Rincon-Limas, Diego E. |
author_facet | Varte, Vanlalrinchhani Munkelwitz, Jeremy W. Rincon-Limas, Diego E. |
author_sort | Varte, Vanlalrinchhani |
collection | PubMed |
description | Alzheimer’s disease (AD) is the most prevalent neurodegenerative dementia in older adults worldwide. Sadly, there are no disease-modifying therapies available for treatment due to the multifactorial complexity of the disease. AD is pathologically characterized by extracellular deposition of amyloid beta (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Increasing evidence suggest that Aβ also accumulates intracellularly, which may contribute to the pathological mitochondrial dysfunction observed in AD. According with the mitochondrial cascade hypothesis, mitochondrial dysfunction precedes clinical decline and thus targeting mitochondria may result in new therapeutic strategies. Unfortunately, the precise mechanisms connecting mitochondrial dysfunction with AD are largely unknown. In this review, we will discuss how the fruit fly Drosophila melanogaster is contributing to answer mechanistic questions in the field, from mitochondrial oxidative stress and calcium dysregulation to mitophagy and mitochondrial fusion and fission. In particular, we will highlight specific mitochondrial insults caused by Aβ and tau in transgenic flies and will also discuss a variety of genetic tools and sensors available to study mitochondrial biology in this flexible organism. Areas of opportunity and future directions will be also considered. |
format | Online Article Text |
id | pubmed-10150963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101509632023-05-02 Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools Varte, Vanlalrinchhani Munkelwitz, Jeremy W. Rincon-Limas, Diego E. Front Neurosci Neuroscience Alzheimer’s disease (AD) is the most prevalent neurodegenerative dementia in older adults worldwide. Sadly, there are no disease-modifying therapies available for treatment due to the multifactorial complexity of the disease. AD is pathologically characterized by extracellular deposition of amyloid beta (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Increasing evidence suggest that Aβ also accumulates intracellularly, which may contribute to the pathological mitochondrial dysfunction observed in AD. According with the mitochondrial cascade hypothesis, mitochondrial dysfunction precedes clinical decline and thus targeting mitochondria may result in new therapeutic strategies. Unfortunately, the precise mechanisms connecting mitochondrial dysfunction with AD are largely unknown. In this review, we will discuss how the fruit fly Drosophila melanogaster is contributing to answer mechanistic questions in the field, from mitochondrial oxidative stress and calcium dysregulation to mitophagy and mitochondrial fusion and fission. In particular, we will highlight specific mitochondrial insults caused by Aβ and tau in transgenic flies and will also discuss a variety of genetic tools and sensors available to study mitochondrial biology in this flexible organism. Areas of opportunity and future directions will be also considered. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10150963/ /pubmed/37139514 http://dx.doi.org/10.3389/fnins.2023.1184080 Text en Copyright © 2023 Varte, Munkelwitz and Rincon-Limas. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Varte, Vanlalrinchhani Munkelwitz, Jeremy W. Rincon-Limas, Diego E. Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title | Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title_full | Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title_fullStr | Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title_full_unstemmed | Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title_short | Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
title_sort | insights from drosophila on aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150963/ https://www.ncbi.nlm.nih.gov/pubmed/37139514 http://dx.doi.org/10.3389/fnins.2023.1184080 |
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