Multiomic profile integration reveals early disease signatures of Amyotrophic lateral sclerosis
This presentation provides an overview of a study comparing mouse models to human data, focusing on pre-symptomatic stages to analyze the prefrontal cortex. The TDP-43D3 mice, which can live up to 120 weeks, and the more aggressive C9R72 mouse model were used.
The study identified sex-specific differences in both mice and humans. Proteomics analysis detected an average of 2,344 proteins per sample, revealing significant deregulations similar to those found in transcriptomics. Common pathways, such as the MAPK pathway, were consistently observed across various analyses, from transcriptomics to proteomics. The study employed a biologically motivated approach to identify valid interactors and validated findings in the lab using mouse models.
Phosphoproteomics and quadruplets analysis further identified important candidates like sequestosome, linked to autophagy. Synaptic and cytoskeletal dysfunctions were noted in both mouse and human samples. Cell type deconvolution based on transcriptomics data was also performed. The results consistently highlighted the MAPK pathway and synaptic compartments, guiding future validation steps. The findings have been recently published for further reference.
Learning points:
- Pre-symptomatic Analysis in ALS Research
- Sex-specific Differences and Pathway Consistency
- Validation and Functional Implications
Who should attend:
- Neuroscientists and Researchers: Those focused on ALS and other neurodegenerative diseases would gain insights into early disease mechanisms and potential therapeutic targets.
- Pharmaceutical and Biotech Companies: Entities involved in drug development for neurodegenerative diseases might benefit from the identified pathways and molecular targets, aiding in the development of new therapies.
