Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases data set
Data files
Feb 14, 2025 version files 91.73 MB
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Figure_1_raw_data_collection.zip
11.85 MB
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Figure_2_Raw_data_collection.zip
13.16 MB
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Figure_3_raw_data_collection.zip
12.47 MB
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Figure_4_raw_data_collection.zip
14.48 MB
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Figure_5_collection_of_raw_data.zip
5.96 MB
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Figure_6_-_collection_of_raw_data.zip
32.63 MB
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Figure_7-Proposed_mechanism_of_action_for_NU-9.zip
1.16 MB
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README.md
2.21 KB
Abstract
Protein aggregation is a hallmark of neurodegenerative diseases, which connects these neuropathologies by a common phenotype. Various proteins and peptides form aggregates that are poorly degraded, and their ensuing pathological accumulation underlies these neurodegenerative diseases. Similarities may exist in the mechanisms responsible for the buildup of these aggregates. Therefore, therapeutics designed to treat one neurodegenerative disease may be beneficial to others. In ALS models, the compound NU-9 was previously shown to block neurodegeneration produced by aggregation-inducing mutations of SOD-1 and TDP-43 [B. Genç et al., Clin. Transl. Med. 11, e336 (2021)]. Here, we report that NU-9 also prevents the accumulation of amyloid beta oligomers (AβOs), small peptide aggregates that are instigators of Alzheimer’s disease neurodegeneration [M. Tolar et al., Int. J. Mol. Sci. 22, 6355 (2021)). AβO buildup was measured by immunofluorescence imaging of cultured hippocampal neurons exposed to exogenous monomeric Aβ. In this model, AβO buildup occurs via cathepsin L- and dynamin-dependent trafficking. This is prevented by NU-9 through a cellular mechanism that is cathepsin B- and lysosome-dependent, suggesting that NU-9 enhances the ability of endolysosomal trafficking to protect against AβO buildup. This possibility is strongly supported by a quantitative assay for autophagosomes that shows robust stimulation by NU-9. These results contribute additional understanding to the mechanisms of protein aggregation and suggest that multiple neurodegenerative diseases might be treatable by targeting common pathogenic mechanisms responsible for protein aggregation.
https://doi.org/10.5061/dryad.0000000dn
Description of the data and file structure
We have submitted our raw data with file names corresponding to the Figure number and subset as well as descriptive titles. The data has been uploaded in (.zip) files, one for each figure of the manuscript. The (.zip) files include (.png) and (.tif) image files and GraphPad Prism files (.pzfx)
This data set contains the raw confocal fluorescence images used for Figures 1-6. Images were collected on a Leica SP5 or Leica SP8 confocal microscope using the Leica software. Images to be presented in the various figures were extracted as (.tif) files. Graph files, and some fluorescence images were saved as (.png) files. All files were combined using Photoshop software into the final figures found in the associated manuscript. Image names correspond to the experimental conditions and date of data collection.
This data set also contains raw dot-blot data images for Figure 2. This data was collected using a Sapphire Imager. Data are presented as un-processed (.tif) files in the Figure 2 dataset (Figure 2 Raw data collection.zip).
Figure 1 raw data files:
(Figure 1 raw data collection.zip)
Figure 2 raw data files:
(Figure 2 Raw data collection.zip)
Figure 3 raw data files:
(Figure 3 raw data collection.zip)
Figure 4 raw data files:
(Figure 4 raw data collection.zip)
Figure 5 raw data files:
(Figure 5 collection of raw data.zip)
Figure 6 raw data files:
(Figure 6 - collection of raw data.zip)
Figure 7 raw data file:
(Figure 7-Proposed mechanism of action for NU-9.zip)
Code/software
Data was analyzed using ImageJ software (free from NIH). Data collected from ImageJ analysis was graphed for publication using Excel (Microsoft Corp) and/or Prism (GraphPad).
Immunofluorescence images were collected using Leica Software (LAS X freeware available from Leica Microsystems). Selected images were saved as TIFF files using the LAS X software.