Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann–Pick Disease Type C
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Transcriptome Analysis
2.3. Data Pre-Processing
2.4. Differential Gene Expression Analysis
2.5. Pathway Enrichment
2.6. Gene Set Enrichment Analysis
3. Results
3.1. Interferon Signaling Is Higher in the Cerebellum Than in the Cerebral Cortex in NPC
3.2. Inflammatory Pathways Linked to DAMP Generation, Excessive ROS, and Lipid Peroxidation in the Npc1−/− Brain Are More Active in the Cerebellum
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A. Expanded Figures to Enhance Readability of Figure 1, Figure 2, Figure 3, Figure 4, Figure 5 and Figure 6. Figure 1 and Figure 3, Figure 4, Figure 5 and Figure 6 Include Heatmaps of Core Enriched Genes for Each Comparison Panel
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Upstream Regulator | Npc1−/− vs. Npc1+/+ | ||
---|---|---|---|
Z-Score | p-Overlap | # Target | |
IFN-γ | 4.104 | 5.12 × 10−11 | 84 |
M-CSF/CSF1 | 3.785 | 6.17 × 10−6 | 21 |
GM-CSF/CSF2 | 3.598 | 1.00 × 10−5 | 33 |
IL-33 | 3.036 | 1.22 × 10−3 | 17 |
TNFα | 2.908 | 9.37 × 10−9 | 96 |
IL-4 | 2.902 | 1.68 × 10−6 | 57 |
IL-6 | 2.737 | 4.26 × 10−6 | 46 |
IL-3 | 2.460 | 3.66 × 10−3 | 21 |
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Tolan, A.J.; Sanchez, K.L.; Shin, S.D.; White, J.B.; Currais, A.; Soriano-Castell, D.; Wilson, C.G.; Maher, P.; Soriano, S. Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann–Pick Disease Type C. Genes 2024, 15, 101. https://doi.org/10.3390/genes15010101
Tolan AJ, Sanchez KL, Shin SD, White JB, Currais A, Soriano-Castell D, Wilson CG, Maher P, Soriano S. Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann–Pick Disease Type C. Genes. 2024; 15(1):101. https://doi.org/10.3390/genes15010101
Chicago/Turabian StyleTolan, Andrew J., Kayla L. Sanchez, Samuel D. Shin, Jacob B. White, Antonio Currais, David Soriano-Castell, Christopher G. Wilson, Pamela Maher, and Salvador Soriano. 2024. "Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann–Pick Disease Type C" Genes 15, no. 1: 101. https://doi.org/10.3390/genes15010101