Amyotrophic Lateral Sclerosis Research

Neuro-glial lipid imbalance in a Drosophila model of Amyotrophic Lateral Sclerosis 8

This study identifies lipid imbalance in a Drosophila ALS8 model, showing that VAPB activity regulates lipid homeostasis in neurons and glia.

SFPQ dysregulation promotes TDP-43 pathology through a pathogenic feedback loop

This study identifies SFPQ as a contributor to TDP-43 pathology through a bidirectional feedback loop, showing SFPQ dysregulation drives TDP-43 mislocalization and aggregation.

HSC70 prevents TDP-43 nuclear puncta formation and toxicity in a novel nuclear puncta cell model for ALS

This paper identifies a TDP-43 mutation, G148V, that causes nuclear puncta formation and toxicity, and shows HSC70 prevents this pathology in a cellular model of ALS.

Schwann Cell-Specific TDP-43 Rescue Improves Peripheral Nerve Myelin Pathology Without Altering Motor Behaviour in a Mouse Model of ALS

This study shows that rescuing Schwann cells in an ALS mouse model improves myelin structure but not motor function, highlighting the complex role of Schwann cells in disease progression.

Transcriptional pathways of definitive ALS genes implicate novel disease-associated target genes

The paper identifies novel disease-associated target genes by analyzing transcriptional pathways linked to definitive ALS genes using RNA sequencing and single-nuclei transcriptomics.

SNRNP70 interacts with TDP-43 to promote RNP granule localisation and regulate motor neuron development

This study identifies a functional interaction between SNRNP70 and TDP-43 that is essential for motor neuron development and regulates RNP granule assembly.

Astrocyte dysfunction distinguishes monozygotic twin C9orf72 expansion carriers discordant for amyotrophic lateral sclerosis.

This study identifies distinct astrocyte states in C9orf72 expansion carriers discordant for ALS, linking epigenetic changes, stress, and functional dysfunction to disease onset.

Modulation of retroviral capsid assembly halts ARC-mediated TDP-43 intercellular spreading

This study shows that ARC acts as a retroviral-like capsid for TDP-43 spreading in ALS and FTD, and that Lenacapavir blocks this process.

Transplantation of Human IPSC-derived Microglia Ameliorates Neuropathology and Circuit Dysfunction in Progranulin-Deficient Mice

This study shows that transplanting wild-type human iPSC-derived microglia into progranulin-deficient mice reduces neuropathology, circuit dysfunction, and behavioral issues in a FTD model.

The folding, dimerization and allosteric landscapes of the ALS protein SOD1: a comprehensive mutational atlas

This study maps the mutational landscape of SOD1 by analyzing monomer folding and dimerization, identifying protein destabilization as a key driver of ALS and uncovering potential therapeutic targets.

TAF15 amyloids propagate via defined motifs in a prion-like fashion

This study shows TAF15 forms amyloid fibrils and propagates prion-like between cells, identifying specific motifs that drive its aggregation in vitro and in cells.

Muscle spatial lipidomics identifies early ALS signatures in presymptomatic SOD1G93A mice

The paper identifies early ALS-related lipid changes in presymptomatic SOD1G93A mice using lipid imaging mass spectrometry, showing sex-dependent and fiber-type-specific alterations detectable before symptoms.

ESCRT Machinery Dysfunction in Motor Neurone Disease: TSG101, CHMP2B, and VPS4a Differentially Regulate TDP-43 Pathology, Autophagy, and Exosome Biogenesis

GDF5 as a Multimodal Protector of the Motor Unit in Amyotrophic Lateral Sclerosis

This study identifies GDF5 as a protective factor in ALS by restoring SMAD signaling and preserving motor unit integrity through gene delivery in a mouse model.

RNA dysregulation and compromised neuronal identity drive pathogenesis in Senataxin-associated ALS

This study investigates how SETX mutations in ALS4 lead to RNA dysregulation and neuronal dysfunction through TGF-β signaling activation and R-loop metabolism disruption.

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders

The paper identifies a shared TOP1-mediated mutagenic mechanism in ALS, FTD, and AD through single-cell genomic analysis and experimental validation.

ADAR2-Mediated RNA Editing Promotes TDP-43 Nuclear Export and Alters RNA Binding

This study shows ADAR2-mediated RNA editing promotes TDP-43 nuclear export and alters its RNA binding, contributing to neurodegenerative disease mechanisms.

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The paper evaluates gene expression-based ALS subtypes across brain and blood tissues using machine learning, finding three subtypes with consistent classification in both tissues.

Lack of motor defects and ALS-like neuropathology in heterozygous Sptlc1 Exon 2 deletion mice

This study creates a mouse model with a heterozygous deletion of Sptlc1 exon 2 and finds no motor defects or ALS-like neuropathology, but homozygous mutants die prematurely.

Intrathecal (G4C2)149 delivery in C9orf72-deficient mice yields mild motor dysfunction and ALS/FTD pathological hallmarks

This paper delivers (G4C2)149 repeats intrathecally in C9orf72-deficient mice, revealing mild motor dysfunction and ALS/FTD pathological features.

Mechanistic Insights into Unfolding of the Mitochondrial Localization Sequence M1 of TDP-43 and Identification of a MAPKAPK2 Inhibitor as a potential binder of M1 for inhibition of TDP-43's Aberrant Mitochondrial Localization

This study investigates the unfolding mechanism of TDP-43's mitochondrial localization sequence M1 and identifies a potential inhibitor, ZINC73240059, that binds M1 to block TDP-43's aberrant mitochondrial localization in ALS.

Multiple motor proteins regulate ALS-linked TDP-43 anterograde axonal transport

The paper investigates TDP-43's anterograde axonal transport in human neurons, revealing its interaction with multiple kinesin motors and implications for ALS pathology.

Chronic diazepam reveals excessive homeostatic gain in SOD1G93A mouse spinal motoneurons

This study shows that SOD1G93A mouse motoneurons exhibit exaggerated homeostatic responses to chronic diazepam inhibition compared to wild-type motoneurons.

Mutant SOD1 expressed by oligodendrocytes aggregates in myelinic nanochannels and accelerates disease progression in familial ALS mice

This study shows that mutant SOD1 aggregates in myelinic nanochannels and accelerates ALS progression in mice, highlighting the role of myelin channel integrity in disease.

Rare neurological and neurodevelopmental variants in ALS link to onset, survival and family history

This study identifies rare neurological and neurodevelopmental variants in ALS patients, showing associations with onset, survival, and family history patterns across two cohorts.

TDP-43 self-assembly is regulated by its disordered NLS-region

This study shows that the disordered NLS-region of TDP-43 is essential for its self-assembly across multiple scales, with a minimal mutation preserving condensation while others reduce it.

Uncovering moonlighting role of mitochondrial presequence translocase machinery in SOD1-mediated ALS pathogenesis

This study identifies a novel interaction between mutant SOD1 and the TIM23 complex in yeast, revealing its role in mitochondrial dysfunction and ALS pathogenesis.

From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology

This study identifies posaconazole as a more effective and safer alternative to ketoconazole for inhibiting TDP-43 pathology in ALS/FTD by reducing aggregation and restoring SREBP2 levels.

Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction

This study identifies TDP-43-dependent cryptic splicing events in synaptic and membrane excitability genes and shows they drive neuronal dysfunction in ALS and FTD.

PAD2 knockout reduces myelin protein aggregates, modulates neuroinflammation and protects motor neurons, axons and neuromuscular junction in a SOD1-ALS mouse model

This study shows that PAD2 knockout reduces protein citrullination, improves motor neuron and axon integrity, and modulates neuroinflammation in a SOD1-ALS mouse model.