| Autor: |
Li F; Institute for Informatics (I2), Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; NeuroGenomics and Informatics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Eteleeb A; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; NeuroGenomics and Informatics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Buchser W; Department of Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Wang G; Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Xiong C; Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Payne PR; Institute for Informatics (I2), Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., McDade E; Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Karch CM; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; NeuroGenomics and Informatics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Harari O; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; NeuroGenomics and Informatics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA., Cruchaga C; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.; NeuroGenomics and Informatics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA. |
| Abstrakt: |
Neuro-inflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, our knowledge of neuro-inflammation is very limited; and the core signaling pathways associated with neuro-inflammation are missing. From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), in this study, we uncovered the core neuro-inflammation signaling pathways in AD. Our novel hypothesis is that weakly activated neuro-inflammation signaling pathways can cause neuro-degeneration in a chronic process; whereas, strongly activated neuro-inflammation often cause acute disease progression like in COVID-19. Using the two large-scale genomics datasets, i.e., Mayo Clinic (77 control and 81 AD samples) and RosMap (97 control and 260 AD samples), our analysis identified 7 categories of signaling pathways implicated on AD and related to virus infection: immune response, x-core signaling, apoptosis, lipid dysfunctional, biosynthesis and metabolism, and mineral absorption signaling pathways. More interestingly, most of genes in the virus infection, immune response and x-core signaling pathways, are associated with inflammation molecular functions. Specifically, the x-core signaling pathways were defined as a group of 9 signaling proteins: MAPK, Rap1, NF-kappa B, HIF-1, PI3K-Akt, Wnt, TGF-beta, Hippo and TNF, which indicated the core neuro-inflammation signaling pathways responding to the low-level and weakly activated inflammation and hypoxia, and leading to the chronic neuro-degeneration. The core neuro-inflammation signaling pathways can be used as novel therapeutic targets for effective AD treatment and prevention. |
