Changing faces of stress: Impact of heat and arsenite treatment on the composition of stress granules

Frydrýšková, Klára; Mašek, Tomáš; Pospíšek, Martin

doi:10.1002/wrna.1596

Cited by 16 publications

(10 citation statements)

References 184 publications

(441 reference statements)

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“…Here we find that iPSC-derived MNs exposed to heat stress, as opposed to hyperosmolarity or oxidative stress, closely recapitulate the phenotypes of ALS MN cultures captured by several classifiers. This result suggests that heat stress more closely approximates ALS pathogenesis compared to osmotic and oxidative stressors, which is in line with previous studies in yeast implicating heat stress as being relevant to the study of neurodegeneration 40 . In particular, our study demonstrates the ability of heat stress to induce subtle ALS-related cellular changes associated within the neuritome compartment and within the FUS fluorescent images.…”

Section: Alssupporting

confidence: 91%

Image-based deep learning reveals the responses of human motor neurons to stress and ALS

Verzat

Harley

Patani

et al. 2021

Preprint

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Although morphological attributes of cells and their substructures are recognized readouts of physiological or pathophysiological states, these have been relatively understudied in amyotrophic lateral sclerosis (ALS) research. In this study we integrate multichannel fluorescence high-content microscopy data with deep-learning imaging methods to reveal - directly from unsegmented images - novel neurite-associated morphological perturbations associated with (ALS-causing) VCP-mutant human motor neurons (MNs). Surprisingly, we reveal that previously unrecognized disease-relevant information is withheld in broadly used and often considered generic biological markers of nuclei (DAPI) and neurons (III-tubulin). Additionally, we identify changes within the information content of ALS-related RNA binding protein (RBP) immunofluorescence imaging that is captured in VCP-mutant MN cultures. Furthermore, by analyzing MN cultures exposed to different extrinsic stressors, we show that heat stress recapitulates key aspects of ALS. Our study therefore reveals disease-relevant information contained in a range of both generic and more specific fluorescent markers, and establishes the use of image-based deep learning methods for rapid, automated and unbiased testing of biological hypotheses.

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Section: Alssupporting

confidence: 91%

Image-based deep learning reveals the responses of human motor neurons to stress and ALS

Verzat

Harley

Patani

et al. 2021

Preprint

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“…AD is a chronic, progressive, and persistent neurodegenerative disease whose main symptoms are reduced motor and cognitive function and accelerated memory loss, resulting from the progressive loss of neurons and synapses in the cerebral cortex, ultimately leading to death [ 66 ].…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Salman

Al-Obaidi

Kitchen

et al. 2021

IJMS

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Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.

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“…Finally, differences in the reported occurrence of γ-H2AX•IL-1α foci might be caused by differences in the cell lines used, high intracellular levels of the transiently produced proteins, usage of endogenous IL-1α versus EGFP-tagged IL-1α which was used in the previous experiments 33 and/or other variations in experimental parameters. Differences in experimental conditions, protein overproduction and various fusion tags have often been shown to have a remarkable effect on the assembly of various protein-protein and protein-nucleic acid complexes, which has been deeply studied, e.g., in the case of stress granules and processing bodies 71 . Etoposide can also provoke cellular responses in additional ways beyond topoisomerase II poisoning; etoposide can induce the production of reactive oxygen species 72 and/ or change the secondary structure of histone H1 73 .…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1α associates with the tumor suppressor p53 following DNA damage

Novak

Zámostná

Vopálenský

et al. 2020

Sci Rep

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identified the previously unreported interaction of IL-1α with the tumor suppressor p53 in both malignant and noncancerous mammalian cell lines and provide evidence that IL-1α can closely colocalize with p53 in both the nucleus and cytoplasm of mammalian cells. Furthermore, this interaction was enhanced by treatment with the DNA-damaging drug etoposide. Results p53 and IL-1α colocalize in both the cell nucleus and cytoplasm. To analyze the subcellular distribution of IL-1α and p53 in mammalian cells and their potential to colocalize, we employed the A375 human malignant melanoma cell line. Endogenous proteins were observed using indirect immunofluorescence and confocal microscopy. Whereas a nuclear distribution of IL-1α and p53 was predominant in our experiments, some signal corresponding to these proteins was regularly detected in the cytoplasm. Data analysis using the ImageJ RGB profiler plugin suggested that a fraction of the p53 and IL-1α populations colocalize in certain regions (Fig. 1). The Pearson's colocalization coefficient computed using the Coloc2 Fiji plugin also suggested the modest colocalization (r = 0.464) of both proteins. We observed the similar behavior of both proteins in the HeLa human cervical cancer cell line and U2OS human osteosarcoma cell line as well (Supplementary Fig. 1).

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Changing faces of stress: Impact of heat and arsenite treatment on the composition of stress granules

Cited by 16 publications

References 184 publications

Image-based deep learning reveals the responses of human motor neurons to stress and ALS

Image-based deep learning reveals the responses of human motor neurons to stress and ALS

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Interleukin-1α associates with the tumor suppressor p53 following DNA damage

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