Amyotrophic Lateral Sclerosis Research

Dysregulated expression of inflammasome and extracellular matrix genes in C9orf72-ALS/FTD microglia

This study identifies dysregulated ECM and inflammasome genes in C9orf72-HRE microglia, linking them to non-cell autonomous neurodegeneration in ALS/FTD.

TDP-43 Aggregate Seeding Impairs Autoregulation and Causes TDP-43 Dysfunction

This study shows that TDP-43 aggregation through prion-like seeding impairs its autoregulation, leading to dysfunction and loss of function in cells.

Generation of C9orf72 repeat knock-in iPSC lines for modelling ALS and FTD

The paper describes the generation and validation of C9orf72 repeat expansion knock-in iPSC lines for ALS and FTD research, showing they differentiate into neurons and display disease-related pathologies.

Generation of C9orf72h370 mice, an intron 1 humanised C9orf72 repeat-expansion knock-in model

The paper generates a mouse model with a humanised C9orf72 repeat expansion to study ALS and FTD, and demonstrates a method for creating such repeat expansions in genomic sequences.

Mutations in SOD1 induce ALS-related phenotypes in 3D iPSC-derived motor neuron (MN) spheroids

This study uses 3D iPSC-derived motor neuron spheroids with SOD1 mutations to show ALS-related phenotypes and genetic variability effects.

The genetics of TDP43-Type-C neurodegeneration: a whole genome sequencing study

This study uses whole genome sequencing and AI to identify genetic variants associated with TDP43-Type-C neurodegeneration, finding novel links to FIG4, UBQLN2, INPP5A, and ANXA11.

Individualized Phenotyping of Functional ALS Pathology in Sensorimotor Cortex

This study uses 7T-fMRI to identify functional connectivity patterns in ALS patients that predict disease onset and progression, showing that disease-defining regions are not always the first behaviorally affected areas.

Title: Cell-autonomous and non-cell-autonomous effects of TRIM72 on ALS disease progression

This study identifies TRIM72's protective role in ALS through both cell-autonomous and non-cell-autonomous mechanisms, showing its therapeutic potential in animal models and human patients.

Dual-targeting CRISPR-CasRx reduces C9orf72 ALS/FTD sense and antisense repeat RNAs in vitro and in vivo

This study demonstrates that CRISPR-CasRx reduces C9orf72 repeat RNAs and DPRs in vitro and in vivo, suggesting its therapeutic potential for ALS/FTD.

Whole blood transcriptome profile identifies motor neurone disease (MND) RNA biomarker signatures

The paper identifies RNA biomarker signatures in whole blood transcriptomes of MND patients compared to controls, highlighting differentially expressed genes and associated molecular pathways.

Opposing roles of p38α phosphorylation and arginine methylation in driving TDP-43 proteinopathy.

This study identifies opposing roles of p38α phosphorylation and arginine methylation in TDP-43 proteinopathy, showing that phosphorylation promotes aggregation while methylation reduces it.

Enhanced in vitro aggregation, but not phase separation, of TDP-43 and its C-terminal fragments generate deep-blue autofluorescence.

This study shows that enhanced in vitro aggregation of TDP-43 and its fragments generates deep-blue autofluorescence, which is not emitted by phase-separated structures or oligomers.

Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons

This study identifies early synaptic dysfunction in ALS patient-derived motor neurons as a mechanism contributing to network-wide structural and functional compensation and vulnerability to neurodegeneration.

Delineating sex-dependent and anatomic decline of motor functions in the SOD1G93A mouse model of amyotrophic lateral sclerosis

This study examines sex-dependent and anatomic differences in motor function decline in SOD1G93A mice, finding males show earlier and less localized onset, and distinct decline rates between sexes.

Examining the potential involvement of NONO in TDP-43 proteinopathy in Drosophila

This study shows that reducing NonA in Drosophila worsens TDP-43-induced pathologies, suggesting a functional link between NONO and TDP-43 in proteinopathy.

Patient-derived Induced Pluripotent Stem Cells as a Model to Study Frontotemporal Dementia Pathologies

This paper shows that undifferentiated patient-derived iPSCs exhibit FTD hallmarks like lysosome dysfunction and TDP-43 proteinopathy, and identifies dysregulated genes related to neurodegeneration.

M102, a combined NRF2 and HSF-1 activator for neuroprotection in amyotrophic lateral sclerosis.

M102, a dual NRF2/HSF1 activator, slows disease progression in 2 mouse models and exerts neuroprotection in human cellular models of ALS.

C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1

This study shows that C9orf72-derived arginine-rich dipeptide repeats enhance G3BP1 phase separation, contributing to ALS and FTD pathology.

The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity

This study identifies DNAJC7 as a mediator of neuroprotection in ALS by modulating HSF1 activity and shows that HSF1 expression can rescue proteotoxic stress in mutant DNAJC7 neurons.

Selective Inhibition of Cytosolic PARylation via PARG99: A Targeted Approach for Mitigating FUS-associated Neurodegeneration

This study investigates PARG99 as a cytosol-specific intervention to reduce FUS-associated toxicity in ALS models while preserving DNA repair.

Axonal transcriptome reveals upregulation of PLK1 as a protective mechanism in response to increased DNA damage in FUSP525L spinal motor neurons

The paper uses compartment-specific RNA-sequencing to analyze axonal and somatodendritic transcriptomes of FUS-ALS motor neurons, identifying PLK1 upregulation as a protective response to DNA damage.

Challenges and promises in optimising a non-clinical protocol of intracerebroventricular human neural stem cell transplantation in ALS

This study evaluates the safety and efficacy of human neural stem cell transplantation in ALS using immunodeficient mice, finding it safe and showing potential therapeutic benefits with prolonged immunosuppression.

ALS-associated FUS mutation reshapes the RNA and protein composition of Stress Granules.

This study examines how ALS-associated FUS mutations alter the RNA and protein composition of Stress Granules in neural cells, revealing molecular changes linked to neurodegeneration.

SOD1 Enzymatic Activity in CSF from ALS patients with and without SOD1 mutations

The paper presents a method to measure SOD1 enzymatic activity in CSF from ALS patients, showing lower activity in mutant SOD1 carriers despite normal protein levels.

C9orf72 expansion creates the unstable folate-sensitive fragile site FRA9A

This paper shows C9orf72 expansions create a folate-sensitive fragile site FRA9A, leading to chromosomal instability and immune responses in patient cells and mice.

A meta-analysis of genetic variant pathogenicity and sex differences in UBQLN2-linked amyotrophic lateral sclerosis and frontotemporal dementia

This paper performs a meta-analysis of UBQLN2 genetic variants in ALS/FTD, finding sex-specific differences in age at onset and aggregate burden in brain tissue.

Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death.

This study shows that skeletal myotubes with ALS-linked mutant SOD1 release factors that cause motoneuron axonopathy and death.

Laminar fMRI in the locked-in stage of amyotrophic lateral sclerosis shows preserved activity in layer Vb of primary motor cortex

This study uses laminar fMRI to show preserved activity in layer Vb of primary motor cortex in a locked-in ALS patient during attempted and passive movements.

ALS-associated RNA binding proteins converge on UNC13A transcription through regulation of REST

The paper shows that three ALS-associated RBPs regulate UNC13A transcription by targeting REST, highlighting their role in synaptic integrity and ALS pathogenesis.

Integrated temporal profiling of iPSCs-derived motor neurons from ALS patients carrying C9orf72, FUS, TARDBP, and SOD1 mutations

This study profiles temporal RNA-seq in iPSC-derived motor neurons from ALS patients with specific mutations, identifying shared gene expression and splicing defects across different mutations.