Introduction
Repurposing drugs for ALS
Disease mechanisms and pathways of ALS
Pathways | ALS | Muscular atrophy | Geneset | ||
---|---|---|---|---|---|
Genes | adjP | Genes | adjP | ||
Signaling by interleukins | 87 | 5.84E−33 | 79 | 5.59E−28 | 472 |
Interleukin-4 and interleukin-13 signaling | 42 | 8.06E−29 | 43 | 1.90E−30 | 108 |
Autophagy | 32 | 4.70E−13 | 28 | 1.29E−10 | 149 |
Selective autophagy | 24 | 4.70E−13 | 20 | 6.80E−10 | 80 |
Interleukin-10 signaling | 19 | 6.14E−13 | 13 | 3.75E−07 | 47 |
Macroautophagy | 30 | 6.14E−13 | 26 | 3.40E−10 | 134 |
Programmed cell death | 37 | 7.69E−13 | 35 | 6.37E−12 | 208 |
FOXO-mediated transcription | 20 | 3.22E−11 | 27 | 2.02E−19 | 65 |
Cellular response to chemical stress | 33 | 7.08E−11 | 34 | 4.85E−12 | 194 |
Apoptosis | 30 | 1.11E−09 | 29 | 1.52E−09 | 179 |
Regulated necrosis | 17 | 1.93E−09 | 14 | 4.14E−07 | 56 |
Purinergic signaling in leishmaniasis | 12 | 5.19E−09 | 9 | 4.81E−06 | 26 |
Cell recruitment (proinflammatory) | 12 | 5.19E−09 | 9 | 4.81E−06 | 26 |
PINK1-PRKN-mediated mitophagy | 11 | 1.03E−08 | 10 | 1.01E−07 | 22 |
Mitophagy | 12 | 2.17E−08 | 11 | 1.49E−07 | 29 |
Defective intrinsic pathway for apoptosis | 11 | 5.08E−08 | 12 | 1.52E−09 | 25 |
TRIF(TICAM1)-mediated TLR4 signaling | 21 | 5.08E−08 | 16 | 3.00E−05 | 108 |
MyD88-independent TLR4 cascade | 21 | 5.08E−08 | 16 | 3.00E−05 | 108 |
Post NMDA receptor activation events | 18 | 6.62E−08 | 8 | 0.036 | 80 |
Diseases of signaling by growth factor receptors and 2nd messengers | 45 | 7.91E−08 | 61 | 2.85E−17 | 433 |
Disease process | Pathways/mechanisms involved |
---|---|
Mitochondrial dysfunction | JAK/STAT pathway |
Pyruvate metabolism | |
Mitochondrial quality control | |
Electron Transport Chain | |
Protein aggregate formation | JAK/STAT pathway |
Protein localisation | |
Autophagy | |
RNA metabolism dysfunction | Nuclear cytoplasmic transport |
RNA splicing | |
Neuroinflammation and glial toxicity | JAK/STAT pathway |
Astrocyte and microglial activation | |
Type 1 IFN activation | |
NK cell activation | |
Denervation and Muscle atrophy | JAK/STAT pathway |
Autophagy | |
IL-6 signalling | |
Activin A/SMAD signalling | |
FOXO3 pathway | |
Excitotoxicity | JAK/STAT pathway |
Synaptic glutamate clearance | |
Glutamate receptor activity | |
Cytoplasmic Ca buffering | |
ER stress | JAK/STAT pathway |
IRE1α/PERK/ATF6 |