Amyotrophic Lateral Sclerosis Research

This study identifies the TBK1-IFNβ-immunoproteasome pathway as a mechanism by which TBK1 reduces TDP-43 aggregation in ALS and FTD.

The paper identifies a multi-protein complex in PBMCs as a target for ALS therapeutic assembly modulators, showing altered composition in ALS patients and responsiveness to treatment.

This study identifies genetic risk factors for FTLD-TDP subtypes using whole-genome sequencing and meta-analysis across multiple cohorts.

This study identifies TDP-43-driven splicing dysregulation as a common mechanism in ALS, FTD, and Alzheimer's disease, linking them through mis-spliced mRNAs like APP.

This study shows C9orf72 ALS mutations cause Nup107 aggregation in motor neurons, leading to pathological changes and reduced lifespan in worm models.

This paper develops a deep learning model using SNP microarray data to predict ALS risk with high accuracy across diverse populations and genotyping platforms.

This study identifies miR-129-5p as a deregulated microRNA in FTD patients, showing its role in astrocyte dysfunction and neurodegeneration.

This study identifies pre-symptomatic TDP-43 pathology in skin and other peripheral organs up to 26.5 years before ALS diagnosis, suggesting skin as a potential biomarker for early detection.

The paper demonstrates that allele-specific siRNA can effectively silence a dominant SETX mutation in ALS4, restoring R-loop levels in patient cells.

This study shows that reducing GPNMB in progranulin-deficient myeloid cells impairs lysosomal function and immune responses, suggesting GPNMB is essential for maintaining immune homeostasis.

The paper identifies context-dependent interactors of TDP-43 that regulate its dysfunction in ALS/FTLD using proximity labeling, mass spectrometry, and snRNA-seq integration.

This study shows that 5-ethynyluridine (5EU) causes nuclear accumulation of TDP-43 and other RNA-binding proteins by altering RNA metabolism and splicing.

The paper identifies neuronal vulnerability to C9orf72 repeat expansion by analyzing transcriptional states in a Drosophila model, finding that Xbp1 expression correlates with resistance to toxicity.

The paper identifies image biomarkers in SOD1-G93A mouse muscle biopsies that track ALS progression from presymptomatic to advanced stages using computational analysis.

This study identifies somatic mutations in ALS genes in the motor cortex of sporadic ALS patients, particularly in excitatory neurons, suggesting a role in disease initiation.

This study shows that FUS-induced splicing changes lead to cytoplasmic accumulation of hnRNP A2b/B1 splice variants, promoting stress granule formation and motor neuron toxicity in a mouse model of ALS.

This study shows that TDP-43 SUMOylation is a stress response that protects neurons, and its disruption is linked to aging and disease.

This study uses simulations to show how charged mutations in FUS affect condensate ageing kinetics by altering β-sheet accumulation and aggregate formation.

This study identifies an RGG peptide that disassembles ALS-associated condensates by reducing toxicity and restoring nuclear localization in FUS mutants.

The paper uses a Graph Neural Network to diagnose ALS with high accuracy and identifies keratin proteins and PT150 as potential biomarkers and therapeutics.

The paper establishes an ALS hiPSC model showing axonal downregulation of neuromuscular junction proteins and identifies FUS binding to their mRNAs.

This paper uses AI to identify gefitinib as a potential ALS treatment, showing it protects motor neurons and reduces TDP-43 fragments in vitro and in vivo.

This study identifies persistent extra-motor behavioural deficits in rNLS8 TDP-43 mice, linked to synaptic gene expression and splicing changes that persist even after motor recovery.

This study uses single molecule microscopy to fingerprint TDP-43 aggregates in brain tissue, distinguishing MND donors from controls and different MND cohorts.

This study introduces DANcer, a deep learning classifier that identifies robust ALS molecular subtypes across bulk and single-cell datasets, showing they correlate with clinical features and cellular mechanisms.

This study identifies citrullination as a novel irreversible post-translational modification of TDP-43 linked to structural changes, aggregation, and pathology in TDP-43 proteinopathies.

This study shows that C9orf72-ALS mutation impairs mitophagy in iNeurons by reducing autophagosome production and ULK1 recruitment to mitochondria.

The paper identifies cell type-specific molecular changes in the prefrontal cortex of C9orf72 ALS/FTD patients correlated with pTDP-43 levels.

The paper identifies reduced PUFA levels in FTD/ALS models and shows neuronal PUFA supplementation improves survival and reduces neuronal death.

This study shows TDP-43 inhibits RNA accumulation in neurites by modulating RNA stability, with ALS mutations causing similar mislocalization.