Amyotrophic Lateral Sclerosis Research

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.

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

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.

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.

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

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.

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.

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.

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

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

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

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.

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.

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

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

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

This study shows that Cx43 hemichannels in astrocytes contribute to ALS progression and that blocking them can protect neurons and improve survival in ALS models.

The paper shows that low-level expression of a pathogenic C-terminally truncated FUS in mice causes transcriptome changes in the spinal cord without motor neuron pathology.

The paper examines axonal transport defects in two ALS mouse models, finding that TDP-43 mutations cause transport issues while FUS mutations do not.

The paper tests antibody and immune-complex responses to neurofilaments and dipeptide-repeats as biomarkers for ALS progression and stratification.

This study uses optogenetic tools to show that TDP-43 oligomerization in zebrafish motor neurons leads to both acute and long-term ALS-related pathologies.

The paper identifies POM121 as a critical nucleoporin affected by C9orf72 repeat RNA, leading to nuclear pore complex disassembly and neuronal toxicity in ALS/FTD.

The paper identifies eRF1 and NMD as modifiers of C9orf72 repeat expansion toxicity by analyzing nucleocytoplasmic proteomic changes in ALS/FTD.

The paper characterizes transcriptional changes in ALS motor cortex, identifying microglial activation and synapse-related pathway alterations as key features.

The paper identifies TRAF6 as an interactor of misfolded SOD1 in ALS, showing it promotes aggregation through ubiquitination.

The paper shows that removing mutant SOD1G37R from corticofugal projection neurons prevents their degeneration but does not affect ALS onset or progression.

This study uses computational methods to identify AIM4's binding site on TDP-43 and shows it inhibits LLPS of a TDP-43 mutant in vitro.

This study shows that an ALS-associated FUS mutation disrupts synaptic vesicle docking and neuromuscular transmission in C. elegans.

This study investigates altered glucose-fatty acid flux in ALS using mouse models and patient-derived myotubes, finding increased fatty acid oxidation linked to slower disease progression but with metabolic heterogeneity across patients.