Amyotrophic Lateral Sclerosis Research

Age-dependent dynamics of neuronal VAPBALS inclusions in the adult brain

This study investigates age-dependent changes in neuronal VAPBALS inclusions in a Drosophila ALS model, showing autophagy's role in aggregate clearance and the impact of TER94 on inclusion density.

Glial state changes and neuroinflammatory RIPK1 signaling are a key feature of ALS pathogenesis

This study identifies glial state changes and RIPK1 signaling as key features of ALS pathogenesis, showing that blocking RIPK1 delays disease onset and modulates glial responses.

Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS

This study examines the effects of HDAC inhibitors and arimoclomol on HSP expression and disease biomarkers in ALS models, finding variable responses across different ALS variants and biomarkers.

Antisense oligonucleotide depletion of CCDC146 is a broad-spectrum therapeutic strategy for ALS

The paper identifies CCDC146 as a modifier of ALS survival through primary cilia dysfunction and shows ASO targeting of CCDC146 rescues ALS phenotypes in human and mouse models.

The nuclear import receptor Kapβ2 protein modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD

This study shows that Kapβ2 protein interacts with poly(GR) and reduces its neurotoxicity in C9orf72-linked ALS/FTD by improving neuron survival.

Large-scale RNA-seq mining reveals ciclopirox triggers TDP-43 cryptic exons

The paper uses large-scale RNA-seq data to show that ciclopirox triggers TDP-43 cryptic exon inclusion through oxidative stress and heavy metal toxicity.

Single-cell profiling of the human primary motor cortex in ALS and FTLD

The paper creates a single-cell atlas of the human primary motor cortex in ALS and FTLD, identifying transcriptional changes and molecular similarities between Betz cells and VENs.

Neurotrauma-induced vulnerability of C9orf72 ALS iPSC-motor neurons revealed by biofidelic stretch injury

This study shows that C9orf72 ALS patient motor neurons are more vulnerable to trauma, with TDP-43 mislocalization and reduced recovery after repeated mild injuries.

Reduced STMN2 and pathogenic TDP-43, two hallmarks of ALS, synergize to accelerate motor decline in mice

This study shows that reduced STMN2 and pathogenic TDP-43 synergize to accelerate motor decline in mice without detectable neuropathology but with mitochondrial abnormalities.

Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations

The paper identifies gene expression patterns in motor neurons that predict ALS across species and SOD1 mutations, revealing differences in vulnerability and resilience.

Rational Design of TDP-43 Derived α-Helical Peptide Inhibitors: an In-Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders

This study uses in-silico methods to design α-helical peptides that inhibit TDP-43 aggregation, identifying candidates with stable structures and high binding affinity for pathological filaments.

Disrupted copper availability in sporadic ALS: Implications for CuII(atsm) as a treatment option

The paper investigates copper availability in sporadic ALS and suggests CuII(atsm) may be therapeutically relevant by improving copper bioavailability.

LINC complex alterations are a hallmark of sporadic and familial ALS/FTD

This study identifies LINC complex alterations as a key feature in ALS/FTD, showing their presence in both genetic and sporadic cases and their correlation with nuclear morphology changes.

Generation of human iPSC-derived phrenic-like motor neurons to model respiratory motor neuron degeneration in ALS

This paper describes a method to generate human phrenic-like motor neurons from iPSCs to model ALS-related respiratory neuron degeneration.

C9orf72 gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types

The paper identifies a C9orf72 gene network correlated with cortical thickness in C9-FTD and implicates vulnerable cell types.

Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats

The paper shows that ribosomal quality control factors reduce toxic repeat-associated non-AUG translation from GC-rich repeats by preventing ribosomal stalling.

PP2A and GSK3 act as modifiers of FUS-ALS by modulating mitochondrial transport

This study identifies PP2A and GSK3 as modifiers of FUS-ALS by modulating mitochondrial transport in Drosophila and human iPSC-derived motor neurons.

PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS

This study evaluates three PERK modulators in an ALS mouse model and finds they do not provide therapeutic benefits, with some effects possibly mediated through PERK-independent mechanisms.

TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43.

This study characterizes a mouse model with TDP-43 M323K mutation, showing cognitive, motor, and structural brain abnormalities linked to TDP-43 mislocalization and increased levels.

Importin-β specific nuclear transport defects recapitulate phenotypic and transcriptional alterations seen in neurodegeneration

The paper shows that Importin-β nuclear transport defects cause TDP-43 mislocalization and transcriptional changes linked to neurodegeneration.

Alterations in Lysosomal, Glial and Neurodegenerative Biomarkers in Patients with Sporadic and Genetic Forms of Frontotemporal Dementia

This study identifies and characterizes lysosomal, glial, and neurodegenerative biomarkers in cerebrospinal fluid and plasma from FTD patients, revealing their correlation with disease severity and tissue changes.

Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons

This study shows that homozygous ALS-linked TARDBP mutations cause synaptic abnormalities and reduced activity in human iPSC-derived motor neurons without affecting TDP-43 localization or aggregation.

ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons

This study shows that the p97 R155H mutation impairs lysophagy in motor neurons, leading to lysosomal dysfunction and reduced viability.

Altered nuclear envelope homeostasis is a key pathogenic event in C9ORF72-linked ALS/FTD

This study identifies altered nuclear envelope homeostasis as a key pathogenic event in C9ORF72-linked ALS/FTD, showing that restoring NE tensional homeostasis can rescue NPC injury and reduce DNA damage.

AAV-based delivery of RNAi targeting Ataxin-2 improves survival, strength, and pathology in mouse models of rapidly and slowly progressive sporadic ALS

ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3'UTR Length

The paper identifies UPF1 targets in motor neurons and shows TDP-43 dysfunction disrupts UPF1-mediated mRNA surveillance and 3'UTR regulation in ALS.

Organellomics: AI-driven deep organellar phenotyping reveals novel ALS mechanisms in human neurons

The paper introduces NOVA, a deep learning model for analyzing organelle structures in neurons, revealing novel ALS mechanisms through phenotypic changes in TDP-43 and P-bodies.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

The paper shows that loss of TDP-43 function leads to the expression of de novo proteins from mis-spliced mRNA transcripts in ALS/FTD.

A functional interaction between TDP-43 and USP10 reveals USP10 dysfunction in TDP-43 proteinopathies

This study identifies a functional interaction between TDP-43 and USP10, showing USP10 modulates alternative splicing and can reduce TDP-43 toxicity in a mouse model of ALS and FTD.

TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes

This study shows that TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes affecting disease-relevant genes.