PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in Drosophila by ATG14L, ATG6/Beclin 1 and VPS34
Version 1
: Received: 19 February 2024 / Approved: 19 February 2024 / Online: 20 February 2024 (06:35:17 CET)
How to cite:
Chuang, C.; Lin, Y.; Tu, Y.; Chi, H.; Sang, T.; Chang, H. Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in Drosophila by ATG14L, ATG6/Beclin 1 and VPS34. Preprints2024, 2024021046. https://doi.org/10.20944/preprints202402.1046.v1
Chuang, C.; Lin, Y.; Tu, Y.; Chi, H.; Sang, T.; Chang, H. Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in Drosophila by ATG14L, ATG6/Beclin 1 and VPS34. Preprints 2024, 2024021046. https://doi.org/10.20944/preprints202402.1046.v1
Chuang, C.; Lin, Y.; Tu, Y.; Chi, H.; Sang, T.; Chang, H. Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in Drosophila by ATG14L, ATG6/Beclin 1 and VPS34. Preprints2024, 2024021046. https://doi.org/10.20944/preprints202402.1046.v1
APA Style
Chuang, C., Lin, Y., Tu, Y., Chi, H., Sang, T., & Chang, H. (2024). Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in <em>Drosophila</em> by ATG14L, ATG6/Beclin 1 and VPS34. Preprints. https://doi.org/10.20944/preprints202402.1046.v1
Chicago/Turabian Style
Chuang, C., Tzu-Kang Sang and Hui-Yun Chang. 2024 "Differential Regulation of Age-Dependent Neurodegeneration and Buildup Human Phosphorylated Tau in Neurons in <em>Drosophila</em> by ATG14L, ATG6/Beclin 1 and VPS34" Preprints. https://doi.org/10.20944/preprints202402.1046.v1
Abstract
Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
