Amyotrophic Lateral Sclerosis Research

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.

This study compares temporal transcriptomic changes in iPSC-derived motor neurons with SOD1 mutations D91A and G94A to understand their impact on ALS severity.

This study shows that N-terminal acetylation of SOD1 increases amyloid formation rate without destabilizing the apo-state structure.

AAV-PHP.eB-CTR gene therapy slows ALS progression and prevents paralysis in symptomatic mice by restoring TDP-43 function.

This study re-expresses embryonic motor neuron factors in mature neurons to reverse age-related degeneration and reduce ALS symptoms in a mouse model.

The paper identifies a circular continuum of alpha-motoneuron types in mice, challenging the traditional linear classification and revealing new subtypes with unique properties.

The paper shows that C9ORF72 repeat expansions cause aberrant splicing, leading to exonization and altered RNA processing in ALS/FTD.

The paper compares TMEM106B pathology in murine models of neurodegenerative diseases to human postmortem tissue, identifying differences and convergent links to TDP-43 and Tau pathology.

This study shows GSDMD is activated in ALS mice but its loss does not improve disease outcomes or reduce neuroinflammation.

The paper identifies MLN4924 as a compound that improves cell viability in TDP-43 mutant motor neurons by targeting NEDD8-activating enzyme.

This study examines how network structure and local biological features influence spatial patterns of cortical atrophy in ALS using the CALSNIC dataset.

The paper identifies cryptic intronic C9orf72 transcripts as endogenous templates for RAN translation, leading to DPR production in ALS/FTD.

The paper identifies two scFv intrabodies that bind to wildtype TDP-43 and show protective effects in a cellular model of TDP-43 proteinopathy.

This study shows that RNA G-quadruplexes influence TDP43 condensation and toxicity in different cell types, suggesting targeting these structures could be a new approach for treating protein misfolding diseases.

This study uses a C. elegans model to show that cytoplasmic TDP-43 causes early functional impairments in serotonergic neurons without neurodegeneration.

The paper identifies microglia subsets in ALS brain and spinal cord, finding an undifferentiated phenotype and enrichment of interferon response microglia in aggressive cases.

This study shows that antisense oligonucleotides targeting VCP reduce disease pathology and improve muscle function in cell and mouse models of multisystem proteinopathy.

This study develops a human model of TDP43 proteinopathy by inducing endogenous TDP43 mislocalization in iPSC-derived neurons, revealing its role in neurodegeneration and splicing defects.

This study examines sex-specific differences in leptin signaling and metabolic regulation in rNLS8 mice with ALS, revealing sex- and stage-dependent changes in expression and pathway activation.

This study shows that FUS RNA condensation regulates its splicing and that disrupting this process can reduce FUS levels, offering a potential therapeutic strategy for ALS-FUS.

The paper identifies co-segregating RUBCN and KANK1 mutations in a UK ALS family, showing their association with disease and functional impact on cellular processes.

This study shows that TDP-43 aggregation in skeletal muscle causes motor dysfunction and neurodegeneration, but clearance of the protein allows for functional recovery.

This study investigates the hnRNP network's role in FTLD-TDP subtypes using single-nuclei RNA-sequencing and immunohistochemistry, finding glial-specific RNA processing changes associated with different pathological subtypes.

This study shows that targeting NMJ regeneration and CXCR4 can improve motor function and survival in ALS models.

This study shows that ALS-linked FUS and SOD1 mutations increase MCM2 protein levels in human motor neurons without affecting its subcellular localization.

The paper identifies molecular components of ALS-associated MetaAggregates using proteomic and in silico methods, revealing 79 candidate proteins and their potential roles in RNA processing and aggregation.

This study measures glutathione oxidation in cerebrospinal fluid of ALS patients and healthy controls, finding elevated levels and correlations with disease progression and protein oxidation.

The paper investigates DNA methylation changes in FTLD risk genes across different subtypes and finds shared hypomethylation in STX6 and other loci, with significant effects in PSP cases.

The paper develops a spiking neural network model of spinal circuits to predict optimal therapeutic windows for ALS intervention by analyzing the effects of V1 interneuron stabilization.

The paper identifies novel cryptic exons in TDP-43 deficient neurons by inhibiting nonsense-mediated decay, revealing potential therapeutic targets for ALS-FTD.