Amyotrophic Lateral Sclerosis Research

Type I PRMT inhibition protects against C9ORF72 arginine-rich dipeptide repeat toxicity

The paper identifies Type I PRMT inhibitors as potential therapeutics for polyGR- and polyPR-related toxicity by showing ADMe of polyGR is critical for its pathogenesis.

Cellular and molecular phenotypes of C9orf72 ALS/FTD patient derived iPSC-microglia mono-cultures

This study examines C9orf72 ALS/FTD patient-derived iPSC-microglia mono-cultures, finding they form RNA foci, have reduced C9orf72 protein, and show endosomal-lysosomal dysfunction, but no significant microglial-enriched gene expression differences.

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

The paper introduces a digital biomarker, Rest Disturbance Index (RDI), to detect rest disturbances in SOD1G93A mice with ALS, showing it correlates with disease progression better than traditional methods.

Properties of Glial Cell at the Neuromuscular Junction are Incompatible with synaptic repair in the SOD1G37R ALS mouse model

The paper shows that glial cells at disease-vulnerable NMJs in SOD1G37R mice fail to support repair mechanisms, leading to impaired compensatory reinnervation.

ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons

This study shows that ALS-FUS mutations disrupt HuD/ELAVL4 and FMRP activities, leading to axon phenotypes in motoneurons through altered transcript stability.

Induction Of Chronic Stress Reveals An Interplay Of Stress Granules And TDP-43 Pathological Aggregates In Human ALS Fibroblasts And iPSC-Neurons

This study shows chronic oxidative stress induces stress granules and TDP-43 aggregates in ALS patient cells, linking SG dysfunction to TDP-43 pathology.

IBD analysis of Australian amyotrophic lateral sclerosis SOD1-mutation carriers identifies five founder events and links sporadic cases to existing ALS families

The carboxyl-termini of RAN translated GGGGCC nucleotide repeat expansions modulate toxicity in models of ALS/FTD

This paper shows that the carboxyl-termini of RAN translated DPRs from GGGGCC repeats affect toxicity in ALS/FTD models, with GR DPRs showing greater toxicity due to their unstructured C-termini.

Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of Amyotrophic Lateral Sclerosis

This study investigates excitability of spinal motoneurones in G93A SOD1 ALS mice and finds no deficits in repetitive firing, but increased input responsiveness and persistent inward currents.

An aberrant cytoplasmic intron retention programme is a blueprint for ALS-related RBP mislocalization

The paper identifies aberrant cytoplasmic intron-retaining transcripts (IRTs) in ALS and shows their association with RBP mislocalization.

Absence of receptor for advanced glycation end product (RAGE) reduces inflammation and extends survival in the hSOD1G93A mouse model of amyotrophic lateral sclerosis

This study shows that removing RAGE signaling in SOD1G93A mice slows ALS progression, extends survival, and reduces neuroinflammation and oxidative stress.

Stress induces cytoprotective TDP-43 nuclear bodies through lncRNA NEAT1-promoted phase separation

The paper shows stress induces TDP-43 nuclear bodies via NEAT1-promoted phase separation, which protects cells from toxicity and is disrupted by an ALS mutation.

C9orf72 dipeptide repeats inhibit UPF1-mediated RNA decay independent of stress granule formation

This study shows that C9orf72 dipeptide repeats inhibit UPF1-mediated RNA decay without requiring stress granule formation, contributing to RNA accumulation in c9ALS/FTD.

Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping

This study uses QSM to assess iron dysregulation in the motor cortex of limb-onset ALS patients over six months, finding increased QSM in lumbar-onset patients compared to controls and no significant change over time.

Caudal-rostral progression of alpha motoneurone degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

The paper quantifies the caudal-rostral progression of alpha motoneurone degeneration in SOD1G93A mice, showing greater susceptibility in lumbar spinal cord regions.

RBM45 associates with nuclear stress bodies and forms nuclear inclusions during chronic cellular stress and in neurodegenerative diseases

This study identifies RBM45's role in forming nuclear inclusions during stress and in neurodegenerative diseases, linking it to nuclear stress bodies and disease-specific pathology.

Synaptic accumulation of FUS triggers age-dependent misregulation of inhibitory synapses in ALS-FUS mice

This study shows that synaptic accumulation of FUS in ALS-FUS mice leads to age-dependent misregulation of inhibitory synapses, suggesting a role in early neurodegeneration.

Tau Accumulation via Reduced BAG3-mediated Autophagy Is Required for GGGGCC Repeat Expansion-Induced Neurodegeneration

This study shows that reduced BAG3-mediated autophagy leads to tau accumulation, contributing to neurodegeneration in Drosophila models of CAG and GGGGCC repeat expansions.

Correction of amyotrophic lateral sclerosis related phenotypes in induced pluripotent stem cell-derived motor neurons carrying a hexanucleotide expansion mutation in C9orf72 by CRISPR/Cas9 genome editing using homology-directed repair

This study corrects a C9orf72 hexanucleotide expansion in iPSC-derived motor neurons using CRISPR/Cas9 and HDR, restoring normal gene expression and eliminating pathological phenotypes.

The cryoEM structure of the fibril-forming low-complexity domain of hnRNPA2 reveals distinct differences from pathogenic amyloid and shows how mutation converts it to the pathogenic form

This paper presents the cryoEM structure of hnRNPA2 LCD fibrils, showing structural differences from pathogenic amyloid and how mutations convert it to a pathogenic form.

Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish

This study investigates the role of NEFL splicing and balance in zebrafish motor neuron development and function, showing that disruption of isoform balance leads to motor deficits and interacts with TDP-43 mislocalization.

Salience network atrophy links neuron type-specific degeneration to loss of empathy in frontotemporal dementia

The paper links neuron type-specific TDP-43 pathology in the frontoinsular cortex to salience network atrophy and loss of empathy in frontotemporal dementia.

TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression

This study identifies CREB signaling as a pathway inhibited by TDP-43 dysfunction, leading to reduced dendritic complexity in neurodegenerative diseases.

CHCHD10 OR CHCHD2 ARE NOT REQUIRED FOR HUMAN MOTOR NEURON DIFFERENTIATION IN VITRO BUT MODIFY SYNAPTIC TRANSCRIPTOMES

CDNF rescues motor neurons in three animal models of ALS by targeting ER stress

This study shows CDNF reduces ER stress and improves motor neuron survival in multiple ALS models, independent of genetic cause.

BioID analysis of the cyclin F interactome reveals that ALS-variant cyclin F alters the homeostasis of paraspeckle-associated proteins

The paper identifies cyclin F interactors using BioID and shows that ALS/FTD-associated cyclin F mutations disrupt paraspeckle protein homeostasis, particularly RBM14 levels in patient tissue.

Analysis of circulating protein aggregates reveals pathological hallmarks of amyotrophic lateral sclerosis

This study identifies circulating protein aggregates as a source of ALS biomarkers and therapeutic targets by showing their enrichment with brain proteins and pathological features.

High content live profiling reveals concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis.

This study shows that C9ORF72 ALS pathogenesis involves both gain and loss of function mechanisms causing axonal organelle trafficking impairment and DNA damage.

FUS gene is dual-coding with both proteins united in FUS-mediated toxicity

The paper identifies an alternative open reading frame (altORF) within the FUS gene that contributes to toxicity in neurodegenerative models.

The homeoprotein ENGRAILED-1 promotes motoneuron survival and motor functions

This study shows that ENGRAILED-1 promotes motoneuron survival and motor function by preventing denervation and neuronal death.