Amyotrophic Lateral Sclerosis Research

White adipose tissue undergoes pathological dysfunction in the TDP-43A315T mouse model of amyotrophic lateral sclerosis (ALS)

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

Glial cell-intrinsic and non-cell autonomous toxicity in a Drosophila C9orf72 neurodegeneration model

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.

Brain Iron as a Surrogate Biomarker of Pathological TDP-43 Identifies Brain Region-Specific Signatures in Ageing, Alzheimer's Disease and Amyotrophic Lateral Sclerosis

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.

Accurate DNA Methylation Predictor for C9orf72 Repeat Expansion Alleles in the Pathogenic Range

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.

LINE1 RNA dysregulation impairs chromatin accessibility in C9ORF72- and TDP-43-linked ALS/FTD

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

Machine learning behavioral analysis reveals cervical instability as an early biomarker of Amyotrophic Lateral Sclerosis

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

Integrative multiomic analysis links TDP-43-driven splicing defects to cascading proteomic disruption of ALS/FTD pathways

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.

Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage

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.

The Impact of Methylglyoxal and SOD1 Mutation on TDP-43 Interaction in ALS Proteinopathy

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

RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability

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

Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons

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.

Single-nucleus transcriptome atlas of orbitofrontal cortex in amyotrophic lateral sclerosis with a deep learning-based decoding of alternative polyadenylation mechanisms

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.

Identifying interactions between TDP-43 N-terminal and RNA binding domains

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

Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells

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.

TDP-43 pathology triggers SRRM4-dependent cryptic splicing of G3BP1 in ALS/FTD

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.

Landscapes of missense variant impact for human superoxide dismutase 1

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.

A validated antibody toolbox for ALS research

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

A point mutation in the nuclear speckle protein and splicing factor SRRM2 is associated with amyotrophic lateral sclerosis and causes dysregulation of synapse-associated genes

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

Induced long-term potentiation improves synaptic stability and restores network function in ALS motor neurons

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

Fast MAS NMR Spectroscopy Can Identify G-Quartets and Double-Stranded Structures in Aggregates Formed by GGGGCC RNA Repeats

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 substantially ameliorate ALS disease in large animal models

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

C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC- Derived Microglia and Modulates Glial-Neuronal Crosstalk

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

Maintenance of neuronal TDP-43 expression requires axonal lysosome transport

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

Targeted degradation of pathogenic TDP-43 proteins in amyotrophic lateral sclerosis using the AUTOTAC platform

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

Early endothelial activation at the blood-nerve barrier defines a hallmark of ALS

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.

Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i3 Neuronal Models of ALS/FTD Pathogenesis

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

Broad brain biodistribution conferred by an AAV to restore TDP-43 function mitigates Frontotemporal Demenia-like deficits

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.

Comparative snRNAseq study of C9orf72, SOD1, and sALS spinal cord

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

Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression

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

An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS

The paper identifies a disease-associated motor neuron state in a mouse ALS model that precedes cell death and links it to human ALS genetic risk factors.