Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

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Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with ...

Proteomics: brain tissues coming from both human PFC and the 4 different mouse models were prepared as follows. Tissues were grinded with a biomasher using 350 µL of MeOH:H2O (4:1). Protein pellets were resuspended in 200 µL Laemmli buffer (10% SDS, Tris 1M pH 6.8, glycerol) then centrifuged at 11.135 rpm at 4°C for 5 minutes. Protein concentration was determined using DC assay (BioRad, Hercules, CA, USA) according to the manufacturer’s instructions. 100 µg of protein lysate for each sample were ...