ArticleNature communications2024
Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
30 citing papers in PubMed.
- Excessive activation of the RAS/MAPK pathway triggers adult-onset motor axonal degeneration.iScience · 2026Article
- Advancement in therapeutic application of quantum dots in amyotrophic lateral sclerosis: current opportunities and challenges.Drug delivery and translational research · 2026Review
- Motor dysfunction phenotypes in a drosophila model validate DAO as an ALS gene.Human molecular genetics · 2026Article
- Chitinases in Tear Fluid of Patients With Amyotrophic Lateral Sclerosis.European journal of neurology · 2026Article
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- Seeing amyotrophic lateral sclerosis in a multi-omic perspective.Neural regeneration research · 2026Article
- Sex-Specific Genetic Architecture of ALS: Evidence of a Female Protective Effect?Annals of neurology · 2026Article
- Superficial white matter microstructural impairments correlate with functional alterations and disease severity in early-stage amyotrophic lateral sclerosis.La Radiologia medica · 2026Article
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Integrative multi-omic analyses identify major axes of heterogeneity in chronic obstructive pulmonary disease and uncover their molecular contributors.medRxiv : the preprint server for health sciences · 2026Article
- Identification of molecular and clinical ALS subgroups based on TDP-43 loss of function molecular markers from population-based patient-derived iPS motor neurons.bioRxiv : the preprint server for biology · 2026Article
- Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.Annals of neurology · 2025Article
- Extracellular Matrix Remodeling in Motor Neuron Diseases.International journal of molecular sciences · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Proteomic analysis of brain and spinal cord tissue reveals distinct immune and mitochondrial processes between human and mouse ALS models.Scientific reports · 2025Article
- Identification and validation of a tear fluid-derived protein biomarker signature in patients with amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study.Neurological research and practice · 2025Article
- TDP-43 pathology is associated with divergent protein profiles in ALS brain and spinal cord.Acta neuropathologica communications · 2025Article
- Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level.Communications biology · 2025Article
Corrections and comments
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Authors and funding
34 authors.
Funding
Abstract
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 the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments.
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Registered trials
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