Amyotrophic Lateral Sclerosis Research

This study investigates how repulsive and attractive crowding environments affect TDP-43 condensates through distinct physical mechanisms and structural dynamics.

The paper investigates WAT dysfunction in TDP-43A315T ALS mice and finds early histological changes and altered leptin levels in human ALS patients.

This study investigates glial cell-intrinsic and non-cell autonomous toxicity in a Drosophila C9orf72 model by expressing different components of the G4C2 repeat expansion.

This study identifies brain region-specific TDP-43 pathology patterns in ageing, Alzheimer's disease, and amyotrophic lateral sclerosis, showing strong correlations with ferritin levels as a potential biomarker.

The paper develops a DNA methylation predictor for C9orf72 repeat expansion carriers using EPICv2 data, achieving 98.6% accuracy and identifying four carriers in an independent cohort.

This study shows that LINE1 RNA dysregulation impairs chromatin accessibility in ALS/FTD, leading to transcriptional changes and neuronal dysfunction.

This paper uses machine learning to detect early cervical instability in ALS mice, identifying it as a behavioral biomarker for early disease detection.

The paper identifies TDP-43-dependent molecular cascades in ALS/FTD by integrating multiomic data from iPSC-derived neurons and validates key genes through experimental assays.

This study shows that iPSC-derived neurons from FTD patients exhibit synaptic dysfunction, DNA damage, and C9-HRE-related pathologies, supporting synaptic dysfunction as a key factor in FTD.

This study investigates how methylglyoxal and G93A SOD1 mutation affect TDP-43 interaction, showing increased cytosolic TDP-43 aggregation and reduced cell viability.

This study shows TDP43 regulates DNA mismatch repair genes, affecting genome stability in neurodegenerative and cancer contexts.

The paper examines changes in chromosome conformation, nuclear organization, and transcription during motor neuron maturation in control and ALS C9orf72 mutant cells, finding delayed maturation in disease models.

The paper constructs a single-nucleus transcriptome atlas of the orbitofrontal cortex in ALS and identifies cell-type-specific transcriptional changes, introducing a deep learning model to analyze alternative polyadenylation.

This study identifies interdomain interactions between the N-terminal and RNA binding domains of TDP-43 using NMR spectroscopy and computational modeling.

This study shows that loss of nuclear TDP-43 in microglia-like cells disrupts lipid metabolism, leading to increased lipid droplets, phagocytosis, and inflammation, which can be mitigated by DGAT inhibitors.

The paper shows that TDP-43 pathology causes a cryptic exon in G3BP1 to be included in neurons, leading to a protein that disrupts stress granule dynamics in ALS/FTD.

The paper measures the functional impact of over two thousand SOD1 missense variants using saturation mutagenesis and cell-based assays, reclassifying 41% of previously uncertain variants as pathogenic.

The paper establishes a validated antibody platform for ALS research, identifying high-quality antibodies and revealing protein expression patterns in neurological cell types.

This study identifies a point mutation in SRRM2 as a risk factor for ALS, showing it disrupts protein interactions and dysregulates synapse-related genes.

This study shows that blocking potassium channels with TEA improves synaptic stability and restores network function in ALS motor neuron networks.

This study uses fast MAS NMR to identify G-quartet and double-stranded structures in GGGGCC RNA aggregates linked to ALS and FTD.

Hypoimmunogenic human motor neurons induced from iPSCs in vivo reform neuromuscular junctions and ameliorate ALS disease in pig and rabbit models.

This study investigates how C9orf72 repeat expansion affects metabolism in human iPSC-derived microglia and its impact on glial-neuronal interactions in ALS.

The paper identifies BORC as a modifier of TDP-43 protein levels in neurons, showing lysosome transport is required for TDP-43 turnover.

This paper develops AUTOTAC degraders to target and degrade pathogenic TDP-43 aggregates in ALS, showing efficacy in mice and entering clinical trials.

The paper identifies early endothelial activation at the blood-nerve barrier as a key feature of ALS, occurring before CNS vascular changes and motor neuron damage.

This study shows that C9orf72 repeat expansion neurons have altered transcriptomes under different stimulation conditions, revealing activity-dependent gene dysregulation in ALS/FTD.

This study uses a BBB-permeable AAV to deliver CTR and restore TDP-43 function in a mouse model of FTLD-TDP, reducing deficits and neuron loss.

This study compares snRNAseq data from C9orf72, SOD1, and sporadic ALS spinal cords, identifying shared and distinct molecular features across cell types.

The paper identifies immune coordination patterns in ALS patients and develops machine learning models to predict disease onset and progression using mass cytometry data.