Amyotrophic Lateral Sclerosis Research

Wild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation.

This study shows that wild-type FUS rescues ALS-like disease caused by mutant FUS by activating an autoregulatory loop that reduces cytoplasmic mutant FUS levels.

A streamlined CRISPR workflow to introduce mutations and generate isogenic iPSCs for modeling amyotrophic lateral sclerosis

This study introduces a streamlined CRISPR workflow to generate isogenic iPSCs with specific ALS-related mutations for modeling the disease.

Protein disulphide isomerase (PDI) is protective against several types of DNA damage, including that induced by amyotrophic lateral sclerosis-associated mutant TDP-43 in neuronal cells/ in vitro models

This study shows PDI protects neuronal cells from DNA damage caused by etoposide, H2O2, or mutant TDP-43, and localizes to DNA damage sites in the nucleus.

Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS

The paper examines whether blood-spinal cord barrier breakdown correlates with motor neuron loss and TDP-43 proteinopathy in ALS, finding they have distinct regional patterns.

A yeast model of the ALS protein Matrin3 uncovers Hsp90 and its co-chaperone Sti1 as modifiers of misfolding and toxicity

The paper establishes a yeast model of Matrin3, showing it forms inclusions and is toxic, and identifies Hsp90 and Sti1 as modifiers of its misfolding and toxicity.

Loss of nucleoporin Nup50 is a risk factor for amyotrophic lateral sclerosis

The paper identifies NUP50 gene variants and reduced expression as risk factors for ALS through transcriptome-wide association and functional studies.

Neurons undergo pathogenic metabolic reprograming in models of familial ALS

The paper identifies metabolic reprogramming in neurons of familial ALS models, showing impaired glycolytic flux with maintained citric acid cycle activity and normal ATP levels.

Riluzole does not ameliorate disease caused by cytoplasmic TDP-43 in a mouse model of amyotrophic lateral sclerosis

This study shows riluzole does not improve disease outcomes in a mouse model of ALS with cytoplasmic TDP-43 pathology.

Cortical hyperexcitability drives dying forward ALS symptoms and pathology in mice

This study shows that cortical hyperexcitability in mice leads to ALS-like motor symptoms and pathology through a dying-forward mechanism.

Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis

This study shows that inhibiting SRSF1-dependent nuclear export of C9ORF72-repeat transcripts in ALS models protects neurons and identifies key RNA changes involved in disease.

Single-cell multimodal omics and directly reprogrammed neurons to probe reduced penetrance in Frontotemporal Dementia

The paper was withdrawn due to lack of full author consent and is not intended for citation.

Unravelling the effects of disease-associated mutations in TDP-43 protein via molecular dynamics simulation and machine learning

The paper uses molecular dynamics simulation and machine learning to analyze disease-associated mutations in TDP-43 and identifies structural features linked to protein stability and pathogenesis.

Rapid and automated quantification of TDP-43 and FUS mislocalisation for screening of frontotemporal dementia and amyotrophic lateral sclerosis gene variants

This paper develops an automated method to quantify TDP-43 and FUS mislocalization in human cell lines to assess the pathogenicity of FTD and ALS gene variants.

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

This study shows that FUS-ALS mutants form cytoplasmic condensates that alter FMRP phase separation, leading to translation inhibition in motor neurons.

DEFINING THE DIVERSITY OF HNRNPA1 MUTATIONS IN CLINICAL PHENOTYPE AND PATHOMECHANISM

The paper characterizes HNRNPA1 mutations in patients with neurodegenerative diseases, showing varied effects on fibrillization, phase separation, and stress granule dynamics.

SFPQ intron retention, reduced expression and aggregate formation in central nervous system tissue are pathological features of amyotrophic lateral sclerosis

This study examines SFPQ dysregulation in ALS patients, finding increased intron retention, reduced mRNA expression in motor cortex, and cytoplasmic aggregates.

Generation, quality control, and analysis of the first genomically humanised knock-in mice for the ALS/FTD genes SOD1, TARDBP (TDP-43), and FUS

The paper creates genomically humanised knock-in mice for ALS/FTD genes SOD1, TARDBP, and FUS, showing they express human proteins at endogenous levels and are phenotypically normal.

The RNA helicase DHX36/G4R1 modulates C9orf72 GGGGCC repeat-associated translation

This study shows that DHX36 modulates RAN translation from G4C2 repeats, with depletion suppressing and overexpression enhancing translation.

Protein crosslinking as a therapeutic strategy for SOD1-related ALS

This paper demonstrates that a cyclic thiosulfinate cross-linker stabilizes SOD1 variants in vivo, showing efficacy and low toxicity for treating SOD1-related ALS.

TMEM106B modifies TDP-43 pathology in human ALS brain and cell-based models of TDP-43 proteinopathy

This study investigates how TMEM106B and C9orf72 genetic variants influence TDP-43 pathology in ALS and FTLD-TDP, finding TMEM106B modifies TDP-43 aggregation severity.

Proximity-based labeling reveals DNA damage-induced N-terminal phosphorylation of fused in sarcoma (FUS) leads to distinct changes in the FUS protein interactome.

The paper investigates how N-terminal phosphorylation of FUS affects its protein interactome using proximity labeling and mass spectrometry, revealing distinct interactome changes and functional consequences.

NMJ-Analyser: high-throughput morphological screening of neuromuscular junctions identifies subtle changes in mouse neuromuscular disease models

NMJ-Analyser quantifies neuromuscular junction morphology and innervation status in mouse models, identifying structural changes in ALS and peripheral neuropathy with high accuracy.

Non-Coding Genetic Analysis Implicates Interleukin 18 Receptor Accessory Protein 3'UTR in Amyotrophic Lateral Sclerosis

The paper identifies non-coding variants in the IL18RAP 3'UTR that reduce ALS risk by modulating neuro-inflammation through NF-κB signaling in microglia.

Orbitofrontal-hypothalamic projections are disrupted in hypermetabolic murine ALS model and human patients

The paper identifies disrupted orbitofrontal-hypothalamic projections in hypermetabolic ALS mouse models and human patients, linking them to hypermetabolism.

Locomotor deficits in ALS mice are paralleled by loss of V1-interneuron-connections onto fast motor neurons

The paper shows that loss of inhibitory synapses from V1 interneurons onto fast motor neurons precedes ALS progression and contributes to locomotor deficits.

Cytoplasmic accumulation of FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and defects in inhibitory synapses

This study shows that cytoplasmic FUS mislocalization in mice causes behavioral changes and inhibitory synaptic defects without widespread neuronal loss.

Enhanced detection of nucleotide repeat mRNA with hybridization chain reaction

This study compares hybridization chain reaction (HCR) to FISH for detecting repeat RNA foci in neurodegenerative disorders, finding HCR to be significantly more sensitive.

Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition

This study uses a microfluidic model of human motor units to show that FUS mutations impair neurite outgrowth and NMJ formation, which can be mitigated by HDAC6 inhibition.

Identification of hub molecules of FUS-ALS by Bayesian gene regulatory network analysis of iPSC model: iBRN

The paper uses iBRN to identify hub molecules in FUS-ALS, finding miR-125b-5p-TIMELESS and PRKDC as key regulators of DNA repair and stress granule formation.

C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility

This study shows that C9orf72 repeat expansions produce toxic arginine-rich DPRs that disrupt axonal transport by interacting with microtubules and motor proteins, contributing to ALS/FTD.