Amyotrophic Lateral Sclerosis Research

ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties

The paper identifies an exitron in UBQLN2 that generates an alternatively spliced isoform with distinct properties linked to ALS.

Dysregulation of LINGO1 expression in the SOD1(G93A) mutant mice during symptomatic stages of the disease and early postnatal oligodendrogenesis

This study shows LINGO1 is upregulated in SOD1(G93A) mice during ALS progression and early oligodendrogenesis, with miR-138 downregulation, suggesting potential therapeutic targets for ALS.

A Human Neuronal Cell Model of Endogenous TDP-43 A315T Reveals Altered Protein Dynamics and Disease-Relevant Cellular Dysfunction

This study develops a human neuronal model with the TDP-43 A315T mutation to study ALS-related protein dysfunction and therapeutic responses.

Defective synapto-nuclear signaling contributes to motoneuron vulnerability in SOD1-ALS

The paper investigates synapto-nuclear signaling defects in mSOD1 mice and shows that restoring cAMP/PKA signaling mitigates pathology in motoneurons.

Assessment of ATXN2 Repeat Expansion Length and Risk of ALS: A Meta-Analysis

This paper conducts a meta-analysis to determine the lower limit of ATXN2 repeat expansions associated with ALS risk, finding that ≥30 repeats define significant risk.

Selective targeting of the oligodendroglial GPR17 receptor improves myelin integrity and motor function in female SOD1G93A mice

This study shows that targeting GPR17 in oligodendrocytes improves myelin and motor function in female ALS mice but not males.

Microsecond molecular dynamics of SOD1 variants suggest a structural basis for divergent ALS clinical outcomes

The paper uses molecular dynamics simulations to analyze SOD1 variants and finds that structural stability and conformational rigidity correlate with clinical severity in ALS.

Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.

The paper identifies early molecular, structural, and functional changes in sensory neurons in the SOD1G93A mouse model of ALS, suggesting sensory neuron hyperexcitability as a potential therapeutic target.

Early MATR3 loss and distinct neurodegenerative molecular signatures precede the onset of neuropathology in motor neurons and Purkinje cells of MATR3 S85C knock-in mouse model of ALS

Characterizing shared and distinctive molecular phenotypes across motor regions in ALS with and without TDP-43 pathology in a veteran cohort

The paper identifies senescence-associated molecular states in ALS motor neurons, showing regional and pathological differences but shared senescence features across ALS subtypes.

Acute Viral Infection Accelerates Neurodegeneration in a Mouse Model of ALS

Acute viral infection accelerates ALS progression in SOD1G93A mice by inducing gliosis and metabolic dysregulation, which can be mitigated by anti-inflammatory or antiviral treatments.

Phase separation behavior of TDP-43 governs its protein interactome and regulation of alternative splicing

This study investigates how TDP-43 phase separation affects its protein interactome and regulation of alternative splicing, showing PS-dependent interactions with RNA regulators.

Cellular modifiers of TDP-43 phase transition and cytoplasmic aggregation

This study identifies cellular factors that modulate TDP-43 phase behavior and shows that nuclear export inhibition reduces its aggregation in a brain organoid model.

Breakdown in the synaptic vesicle cycle defines early and reversible cortical pathogenesis in ALS

The paper identifies early synaptic vesicle cycle disruption in ALS using proteomics and shows it is reversible with TDP-43 suppression.

High-Content Screening Identifies Dithiocarbamates As A Class Of Chemicals That Disrupts TDP-43 Proteostasis

This study identifies dithiocarbamates as chemicals that disrupt TDP-43 proteostasis by causing aggregation and loss of function through redox imbalance and zinc homeostasis disruption.

Enrichment of Repeat Expansions in FGF14 Associated with Amyotrophic Lateral Sclerosis

The paper identifies FGF14 GAA repeat expansions in ALS patients, showing enrichment compared to controls and suggesting a broader pathogenic role in motor neuron disease.

Genome-wide analyses reveal shared and distinct genetic architecture linking amyotrophic lateral sclerosis, sporadic frontotemporal dementia and cognitive traits

The paper identifies shared and distinct genetic loci linking ALS, sFTD, and cognitive traits using genome-wide association data.

Quantification of X-chromosome inactivation in fibroblast and iPSC models of UBQLN2 ALS/FTD using allele-selective qPCR

The paper develops an allele-selective qPCR assay to quantify X-chromosome inactivation in iPSC models of UBQLN2 ALS/FTD and identifies clones retaining XCI for further study.

Pathology-defined cell states reveal reproducible transcriptomic signatures across ALS cortical single-nucleus RNA-seq studies

The paper shows that using pathology-defined cell states improves reproducibility of transcriptomic signatures in ALS snRNA-seq studies compared to conventional case-control analyses.

Autophagy induction mitigates FUS aggregate formation and early synaptic dysfunction at the NMJ in the FUS-ALS model

This study shows that inducing autophagy reduces FUS aggregate formation and synaptic dysfunction in an ALS model.

TDP-43 controls RNA structure through high affinity lattice interactions

This study shows TDP-43 binds to GU repeats with high affinity, prevents pUG fold formation, and reveals an interplay between RNA folding and protein recognition.

A disease dynamics atlas forecasts patient states and maps molecular programs in ALS

The paper develops DynaALS, a disease dynamics atlas for ALS that maps patient states and molecular programs using longitudinal medical records and multi-omics data.

Oral administration of dibenzoylmethane (DBM) prevents cognitive decline in a C9ORF72-mediated FTD mouse model

This study shows that oral DBM treatment prevents cognitive decline in a C9ORF72 FTD mouse model without altering protein inclusions but corrects gene expression changes related to cytoskeleton, ALS, and metabolism.

The ALS/FTD-linked protein CHCHD10 associates with the TDP-43 C-terminal domain through a CHCH-helix interface

This study identifies a CHCH-helix interface between CHCHD10 and TDP-43CTD that modulates their assembly equilibria and aggregation behavior.

Distinct Cellular Phenotypes of Language and Executive Decline in Amyotrophic Lateral Sclerosis

The paper maps cognitive impairments in ALS by integrating spatial and single-nucleus transcriptomics, revealing distinct cellular and molecular patterns in language and executive dysfunction.

ZDHHC17 Links S-Acylation, Huntington Disease, VCP-associated Multisystem Proteinopathy, and Amyotrophic Lateral Sclerosis.

This study identifies ZDHHC17 as a key enzyme linking S-acylation to neurodegenerative diseases by modulating protein localization and toxicity.

ROMO1 loss in cholinergic neurons induces mitochondrial ultrastructural damage and ALS-like neuromuscular degeneration

This study shows that loss of ROMO1 in cholinergic neurons causes mitochondrial damage and ALS-like symptoms in mice.

AAV-Delivered Anti-PC-OxPL Antibody Fragments: A NovelTherapeutic Approach to Target ALS

This paper develops an AAV-delivered scFv antibody targeting PC-OxPL to reduce neurotoxicity and motor neuron death in ALS models.

A Phosphorylation-Induced Micellization switch in the low complexity domain of TDP-43

This study shows phosphorylation of TDP-43's low-complexity domain shifts its self-assembly from macrophase separation to micellization, potentially protecting against pathological aggregation.

A multi-omics characterization reveals distinct molecular signatures in the human motor cortex and lumbar spinal cord in ALS

This study uses multi-omics data to compare molecular signatures in the motor cortex and lumbar spinal cord of ALS patients, finding distinct alterations in MN and glial functions depending on symptom onset site.