ArticleCurrent Alzheimer research2011
Changes in the expression of the Alzheimer’s disease-associated presenilin gene in drosophila heart leads to cardiac dysfunction.
Article in Current Alzheimer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Analysis of hidradenitis suppurativa-linked mutations in four genes and the effects of PSEN1-P242LfsX11 on cytokine and chemokine expression in macrophages.Human molecular genetics · 2019Pooled it
- Dual color optogenetic tool enables heart arrest, bradycardic, and tachycardic pacing in Drosophila melanogaster.Communications biology · 2024Article
- Attention LSTM U-Net model forBiomedical optics express · 2024Article
- Developing Drosophila melanogaster Models for Imaging and Optogenetic Control of Cardiac Function.Journal of visualized experiments : JoVE · 2022Article
- FlyNet 2.0: drosophila heart 3D (2D + time) segmentation in optical coherence microscopy images using a convolutional long short-term memory neural network.Biomedical optics express · 2020Article
- Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment.Molecular neurobiology · 2019Review
- Automated drosophila heartbeat counting based on image segmentation technique on optical coherence tomography.Scientific reports · 2019Article
- Segmentation of Drosophila heart in optical coherence microscopy images using convolutional neural networks.Journal of biophotonics · 2018Article
- Presenilins as Drug Targets for Alzheimer's Disease-Recent Insights from Cell Biology and Electrophysiology as Novel Opportunities in Drug Development.International journal of molecular sciences · 2018Review
- Molecular mechanisms of heart failure: insights from Drosophila.Heart failure reviews · 2017Review
- Drosophila Preparation and Longitudinal Imaging of Heart Function In Vivo Using Optical Coherence Microscopy (OCM).Journal of visualized experiments : JoVE · 2016Article
- The Role of Presenilin in Protein Trafficking and Degradation-Implications for Metal Homeostasis.Journal of molecular neuroscience : MN · 2016Review
- Viewing Extrinsic Proteotoxic Stress Through the Lens of Amyloid Cardiomyopathy.Physiology (Bethesda, Md.) · 2016Review
- Genetic manipulation of cardiac ageing.The Journal of physiology · 2016Review
- Optogenetic pacing in Drosophila melanogaster.Science advances · 2015Article
- A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy.PloS one · 2015Article
- Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.Human molecular genetics · 2013Article
- Space-division multiplexing optical coherence tomography.Optics express · 2013Article
- Presenilin promotes dietary copper uptake.PloS one · 2013Article
- Longitudinal Imaging of Heart Development With Optical Coherence Tomography.IEEE journal of selected topics in quantum electronics : a publication of the IEEE Lasers and Electro-optics SocietyArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer’s disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly reduced heart rate and remarkably age-dependent increase in end-diastolic vertical dimensions. In contrast, overexpression of dPsn increased heart rate. Either overexpression or silencing of dPsn resulted in irregular heartbeat rhythms accompanied by cardiomyofibril defects and mitochondrial impairment. The calcium channel receptor activities in cardiac cells were quantitatively determined via real-time RT-PCR. Silencing of dPsn elevated dIP3R expression, and reduced dSERCA expression; overexprerssion of dPsn led to reduced dRyR expression. Moreover, overexpression of dPsn in wing disc resulted in loss of wing phenotype and reduced expression of wingless. Our data provide novel evidence that changes in presenilin level leads to cardiac dysfunction, owing to aberrant calcium channel receptor activities and disrupted Wnt signaling transduction, indicating a pathogenic role for presenilin mutations in DCM pathogenesis.
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