Amyotrophic Lateral Sclerosis Research

Caspar, an adapter for VAP and TER94, delays the progression of disease by regulating glial inflammation in a Drosophila model of ALS8

The paper shows that Caspar overexpression in glia slows ALS progression by reducing inflammation in a Drosophila model.

Common ALS/FTD risk variants in UNC13A exacerbate its cryptic splicing and loss upon TDP-43 mislocalization

The paper shows that ALS/FTD risk variants in UNC13A increase sensitivity to TDP-43 depletion by promoting cryptic exon inclusion and protein loss.

MRI-guided histology of TDP-43 knock-in mice implicates parvalbumin interneuron loss, impaired neurogenesis and aberrant neurodevelopment in ALS-FTD

This study uses MRI and histology to identify structural and cellular changes in TDP-43 knock-in mice, linking them to ALS-FTD pathology and identifying PV+ interneuron loss as a potential biomarker.

C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent accumulation of Staufen in nucleus

The paper shows that Staufen accumulates in the nucleus in a C9orf72-associated Drosophila model and that reducing Staufen dosage mitigates PR toxicity.

C9ORF72 dipeptide repeat proteins disrupt formation of GEM bodies and induce aberrant accumulation of survival of motor neuron protein

This study shows that dipeptide repeat proteins from C9ORF72 mutations disrupt GEM body formation and cause SMN protein mislocalization in motor neurons.

TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6

The paper identifies TDP-43 proteinopathy's impact on mRNA ribosome association, highlighting Dlp/GPC6 as a novel target in ALS.

Gel-like inclusions of C-terminal fragments of TDP-43 sequester and inhibit proteasomes in neurons

This study identifies TDP-25 inclusions as sequestering proteasomes, leading to proteostasis impairment in ALS/FTD.

Gene co-expression network analysis in human spinal cord highlights mechanisms underlying amyotrophic lateral sclerosis susceptibility

The paper identifies gene co-expression modules in human spinal cord RNA-seq data that are dysregulated in ALS, linking them to specific biological processes and cell types involved in disease.

Single cell transcriptomics identifies master regulators of dysfunctional pathways in SOD1 ALS motor neurons

The paper uses single cell transcriptomics to identify master regulators of dysfunctional pathways in SOD1 ALS motor neurons, finding SMAD2 activation as a key driver of neurodegeneration.

Role of CNC1 gene in TDP-43 aggregation-induced oxidative stress-mediated cell death in S. cerevisiae model of ALS.

The paper investigates the role of CNC1 gene in TDP-43 aggregation-induced oxidative stress-mediated cell death in a yeast model of ALS, finding that CNC1 deletion reduces TDP-43 toxicity.

Time course of alterations in adult spinal motoneuron properties in the SOD1(G93A) mouse model of ALS

The paper shows that spinal motoneurons in ALS mice maintain excitability through homeostasis, but this process pushes some cells beyond normal conductance ranges, potentially contributing to degeneration.

Effect of ozone exposure on Amyotrophic Lateral Sclerosis (ALS) pathology using a mice model of TDP-43 proteinopathy

This study examines the effect of ozone exposure on ALS pathology in a TDP-43A315T mice model, finding altered metabolic profiles and potential improvements in motor performance.

New lessons on TDP-43 from the killifish N. furzeri

This paper demonstrates that TDP-43 paralogs in the killifish N. furzeri form amyloid-like aggregates during ageing, suggesting the fish as a model for TDP-43-related neurodegenerative diseases.

Inhibiting glycogen synthase kinase 3 suppresses TDP-43-mediated neurotoxicity in a caspase-dependant manner

This study shows that inhibiting GSK3 reduces TDP-43 levels and neurotoxicity in mammalian neurons by promoting TDP-43 turnover through a caspase-dependent mechanism.

Diminished miRNA activity is associated with aberrant cytoplasmic intron retention in ALS pathogenesis

The paper identifies cytoplasmic intron-retaining transcripts (IRTs) associated with miRNA activity changes in ALS, showing VCP mutations increase IR and target gene expression.

Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types.

This paper identifies genetic pathways and cell types involved in ALS using polygenic risk scores and Mendelian randomization, finding convergence on specific biological processes and cell types.

Inducible expression of human C9ORF72 36x G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice

This paper introduces a new inducible mouse model expressing C9ORF72 G4C2 repeats that causes RAN translation and muscular atrophy, showing that early intervention can prevent but not reverse the phenotype.

Expression of a miRNA targeting mutated SOD1 in astrocytes induces motoneuron plasticity and improves neuromuscular function in ALS mice

In Vivo Validation of Bimolecular Fluorescence Complementation (BiFC) to Investigate Aggregate Formation in Amyotrophic Lateral Sclerosis (ALS)

The paper validates and optimizes Bimolecular Fluorescence Complementation (BiFC) in zebrafish to study ALS-linked protein aggregate formation in vivo.

Single-cell RNA-seq analysis of human iPSC-derived motor neurons resolves early and predictive ALS signatures

The paper uses single-cell RNA-seq to identify early ALS signatures in iPSC-derived motor neurons across multiple models and platforms.

The novel chaperone protein SRCP1 reduces insoluble SOD1 protein in vivo without extending ALS mouse lifespan

This study shows SRCP1 reduces insoluble SOD1 in ALS models but does not extend mouse lifespan.

Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice

This study shows longer G4C2 repeats in C9orf72 transgenic mice lead to earlier disease onset, higher penetrance, and more RNA foci, with alternative splicing changes as early biomarkers.

TDP-43 deficiency links Amyotrophic Lateral Sclerosis with R-loop homeostasis and R loop-mediated DNA damage

This study shows that TDP-43 deficiency leads to R-loop accumulation and DNA damage, linking ALS pathology to R-loop homeostasis.

Investigations into modifications of neuromuscular physiology by axonal transport disruptions in Drosophila SOD1 mutants

This study investigates how mutations in axonal transport genes modify neuromuscular defects in Drosophila SOD1 mutants, revealing isoform-specific effects on survival and junction morphology.

Increased axon initial segment length results in increased Na+ currents in spinal motoneurones at symptom onset in the G127X SOD1 mouse model of Amyotrophic Lateral Sclerosis.

The paper investigates excitability changes in G127X SOD1 mice at symptom onset, finding increased Na+ currents and longer axon initial segments (AISs) in spinal motoneurones.

ALS Motor Neurons Exhibit Hallmark Metabolic Defects That Are Rescued by Nicotinamide and SIRT3 Activation

This study identifies metabolic defects in ALS motor neurons and shows that nicotinamide and SIRT3 activation can rescue these defects.

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

The paper performs an integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients to identify dysregulated pathways and validate them in vivo and in postmortem data.

TDP-43 proteinopathy impairs neuronal mRNP granule mediated postsynaptic local translation and mRNA metabolism

This study shows TDP-43 localizes to postsynaptic mRNP granules and impairs their dynamics and mRNA metabolism in neurodegenerative disease models.

Amyotrophic lateral sclerosis associated mislocalisation of TDP-43 to the cytoplasm causes cortical hyperexcitability and reduced excitatory neurotransmission in the motor cortex.

This study shows that TDP-43 mislocalization to the cytoplasm in motor cortex neurons causes hyperexcitability and reduced excitatory neurotransmission, linking early ALS pathology to TDP-43 mislocalization.

TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD

This study shows TDP-43 stabilizes G3BP1 transcripts via direct binding, and TDP-43 depletion reduces G3BP1 protein levels, contributing to stress granule dysfunction in ALS/FTD.