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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1184080/full |
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| author | Vanlalrinchhani Varte Jeremy W. Munkelwitz Diego E. Rincon-Limas Diego E. Rincon-Limas Diego E. Rincon-Limas |
| author_facet | Vanlalrinchhani Varte Jeremy W. Munkelwitz Diego E. Rincon-Limas Diego E. Rincon-Limas Diego E. Rincon-Limas |
| author_sort | Vanlalrinchhani Varte |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T17:40:33Z |
| format | Article |
| id | doaj.art-4eeddfa3347749949a6c6e54a3d4675c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-09T17:40:33Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-4eeddfa3347749949a6c6e54a3d4675c2023-04-17T05:48:19ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-04-011710.3389/fnins.2023.11840801184080Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and toolsVanlalrinchhani Varte0Jeremy W. Munkelwitz1Diego E. Rincon-Limas2Diego E. Rincon-Limas3Diego E. Rincon-Limas4Department of Neurology, McKnight Brain Institute, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United StatesDepartment of Neurology, McKnight Brain Institute, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United StatesDepartment of Neurology, McKnight Brain Institute, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United StatesDepartment of Neuroscience, University of Florida, Gainesville, FL, United StatesGenetics Institute, University of Florida, Gainesville, FL, United StatesAlzheimer’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.https://www.frontiersin.org/articles/10.3389/fnins.2023.1184080/fullAlzheimer’s diseaseamyloid betaDrosophilamitochondrianeurodegenerationtau |
| spellingShingle | Vanlalrinchhani Varte Jeremy W. Munkelwitz Diego E. Rincon-Limas Diego E. Rincon-Limas Diego E. Rincon-Limas Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools Frontiers in Neuroscience Alzheimer’s disease amyloid beta Drosophila mitochondria neurodegeneration tau |
| 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 | Alzheimer’s disease amyloid beta Drosophila mitochondria neurodegeneration tau |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1184080/full |
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