Amyotrophic Lateral Sclerosis Research

This study shows that overexpressing the potassium channel subunit Kcnn1 in ALS and alpha-synuclein mouse models extends survival and reduces protein aggregation by inducing stress response pathways.

The paper develops FRET biosensors to monitor TDP-43 N-terminal domain interactions and identifies ketoconazole as a potential drug candidate for ALS and FTD.

The paper identifies a protective variant CREB3R119G that reduces ALS risk and progression by modulating CREB3 activity in vulnerable neurons.

This study investigates the role of antisense and sense repeat RNAs in producing dipeptide repeat proteins in C9ORF72 expansion carriers and shows that targeting sense RNA with ASOs reduces both sense- and antisense-dependent DPR proteins.

The paper tests drug combinations in a TDP43-ALS mouse model to extend lifespan but finds no substantial lifespan extension despite dietary interventions.

This study examines how the prospect of a clinical trial influences decision-making for predictive genetic testing in individuals at-risk for familial ALS, highlighting the role of genetic counseling.

This study shows that hyperexcitability precedes neurodegeneration in a TDP-43 mouse model of ALS-FTD, but targeting hyperexcitability does not prevent neuron loss.

This study identifies FUS's role in muscle differentiation and structure through phase separation-mediated recruitment of ETV5 and MEF2, showing its dysfunction in FUS-ALS.

This study shows proteasome inhibitors reduce FUS aggregation in ALS models through HSF1-dependent transcriptional mechanisms, suggesting a potential therapeutic strategy for ALS-FUS.

Blocking the carboxy terminus of progranulin enhances gene therapy efficacy in progranulin-deficient mice by reducing sortilin interactions and improving biomarker outcomes.

This study identifies FGF21 as a biomarker in ALS associated with slower disease progression and protective effects against stress-induced cytotoxicity.

This study shows that reducing RAD23A in TDP-43 mice improves survival, behavior, and reduces TDP-43 pathology and transcriptomic alterations.

This study investigates the role of KIF5A in axonal transport and repair in human motor neurons, finding that its loss impairs mitochondrial and SFPQ granule transport and axonal regeneration.

This study identifies acetylation of lysine 82 in TDP-43 as a mechanism causing nuclear loss of function and cytoplasmic accumulation, linked to neurodegenerative diseases like ALS.

This study shows that biological sex influences skeletal muscle atrophy in a mouse model of ALS, with sex-specific patterns of muscle vulnerability.

This study shows that the gut microbiota influences sexual dimorphism in ALS-linked TDP43 mice by affecting disease onset and severity, independent of sex hormones.

This study evaluates a mouse model of C9-ALS/FTD, finding it robust for molecular mechanisms but not for neurodegeneration and motor deficits.

This study uses a multimodal cryo-correlative microscopy pipeline to visualize TDP43 mislocalization and aggregation in iPSC-derived neurons and patient tissue, revealing ordered fibrils in autophagosomes and lysosomes.

This study shows that C9orf72 repeat expansion in iPSC-derived microglia from FTD patients leads to increased phagocytic activity and reduced autophagosomal-lysosomal vesicles.

This paper shows that enhancing TARDBP exitron splicing reduces TDP-43 aggregation and neurodegeneration in disease models using ASOs.

This study shows that an enhancer mutation in MEF2C causes mitochondrial dysfunction and motor deficits in mice by impairing mitochondria-encoded gene expression.

The paper introduces CUTS, a biosensor for real-time detection of TDP-43 loss-of-function, showing its sensitivity, accuracy, and potential for gene therapy applications.

This study shows TDP-43 mutations disrupt miRNA biogenesis by affecting Dicer activity, leading to cytotoxicity in Drosophila and in vitro models.

This study identifies Kapβ2 as a target of DPRs, showing how DPR binding alters its phase-modifying function, leading to toxic RBP condensates in ALS models.

This study identifies TDP43 autoregulation as a source of shortened isoforms, showing they are regulated by NMD and post-translational degradation, and their dysregulation leads to neurodegeneration.

This study shows that loss of TDP-43 causes synaptic dysfunction through a cryptic exon in UNC13A, which is rescued by antisense oligonucleotides.

This study identifies TMEM106B C-terminal fragments as aggregating proteins linked to neurodegenerative diseases and shows their toxic effects in a C. elegans model.

The paper shows FDA-approved PDE4 inhibitors reduce mitochondrial defects and toxicity caused by CHCHD10S59L mutations in human cells and Drosophila models.

This study identifies a mechanism by which progranulin deficiency leads to mitochondrial hyperfusion and neuroinflammation in GRN-FTD, showing that targeting C3aR can restore mitochondrial integrity and reduce microglial activation.