Amyotrophic Lateral Sclerosis Research

Comparative Temporal Transcriptomic Analysis of SOD1 Mutations in iPSC-Motor Neurons

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

N-terminal acetylation of superoxide dismutase 1 accelerates amyloid formation without general destabilization of the apo-state

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

Symptomatic treatment by a BBB-permeable AAV engineered to restore TDP-43 function slows motor neuron disease and prevents paralysis

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

Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons

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

Circular continuum of alpha motoneuron types

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

Aberrant splicing exonizes C9ORF72 repeat expansion in ALS/FTD

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

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease

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.

Gasdermin D is activated but does not drive neurodegeneration in SOD1G93A model of ALS: Implications for targeting pyroptosis

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

Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924

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

Network Spreading and Local Biological Vulnerability in Amyotrophic Lateral Sclerosis

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

Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation

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

scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy

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

The effect of G-quadruplexes on TDP43 condensation, distribution, and toxicity

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.

Cytoplasmic TDP-43 leads to early functional impairments without neurodegeneration in a Serotonergic Neuron-Specific C. elegans Model

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

Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord

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

Antisense oligonucleotides targeting Valosin-containing protein improve muscle pathology and molecular defects in cell and mouse models of multisystem proteinopathy.

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

Rapid and Inducible Mislocalization of Endogenous TDP43 in a Novel Human Model of Amyotrophic Lateral Sclerosis

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.

Sex-specific hypothalamic axis disruption in the rNLS8 mouse model of amyotrophic lateral sclerosis (ALS)

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.

FUS post-transcriptional splicing is autoregulated via RNA condensation with therapeutic potential for ALS-FUS

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.

Identification of co-segregating RUBCN and KANK1 mutations in a UK amyotrophic lateral sclerosis kindred

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.

Skeletal muscle TDP-43 aggregation drives progressive motor dysfunction and neurodegeneration with potential for functional recovery after clearance

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

Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in FTLD pathological subtypes

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.

Targeting Neuromuscular Junction Regeneration is a Therapeutic Strategy in ALS

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

ALS-Linked FUS and SOD1 Mutations Elevate MCM2 in Human Motor Neurons

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

Proteomic and in silico dissection of MetaAggregates in amyotrophic lateral sclerosis brains

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.

Glutathione Oxidation in Cerebrospinal Fluid as a Biomarker of Oxidative Stress in Amyotrophic Lateral Sclerosis

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.

DNA methylation as a contributor to dysregulation of STX6 and other frontotemporal lobar degeneration genetic risk-associated loci

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.

Spinal Circuit Mechanisms Constrain Therapeutic Windows for ALS Intervention

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.

Inhibition of nonsense-mediated decay in TDP-43 deficient neurons reveals novel cryptic exons

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

microRNA-206 is a reproducibly sensitive and specific plasma biomarker of amyotrophic lateral sclerosis

The paper identifies hsa-miR-206 as a sensitive and specific plasma biomarker for ALS using small-RNA sequencing and machine learning, validated by ddPCR in an independent cohort.