Amyotrophic Lateral Sclerosis Research

The paper identifies sex-specific risk loci for ALS, including MEF2C, which is upregulated in female ALS motor neurons, and an X-chromosome locus at IL1RAPL2.

The paper isolates and analyzes the proteome of TDP-43-associated insoluble stress granules in an ALS mouse model, identifying sustained stress granule formation, CLUH granule recruitment, and impaired mitochondrial metabolism.

This study shows that VAPB P56S mutation causes mitochondrial dysfunction and enhances the integrated stress response, leading to motor neuron disease in ALS.

This study compares compound muscle action potentials (CMAPs) in SOD1G93A mice and human ALS patients to identify translational alignment points for disease progression.

This study identifies NEK1's role in motor neuron neurite outgrowth by coordinating retromer formation through interactions with SMC3.

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.

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

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.

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

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.

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

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.

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.

The paper shows that energy scarcity and mitochondrial translation impairment cause ALS-FTD-related proteins to form perinuclear stress granule clusters, potentially leading to pathological inclusions.

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

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.

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.

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

This study shows that GRN haploinsufficiency in FTD causes lysosomal and mitochondrial dysfunction, lipid metabolism changes, and autophagy impairment, which may contribute to disease pathogenesis.

The paper identifies TDP-43 dysregulation of polyadenylation site selection as a key feature of RNA misprocessing in ALS/FTD and related disorders, linking it to increased tau phosphorylation.

The paper identifies novel cryptic polyadenylation events induced by TDP-43 loss in ALS/FTD using bioinformatic methods and shows their potential disease relevance and impact on protein translation.

This study tests a novel FKBP12 ligand, MP-010, in ALS mice, showing improved motor function, preserved motor neurons, and extended lifespan.

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

The paper identifies dysregulated expanded endocannabinoid system metabolites in ALS and shows FAAH inhibition improves motor neuron degeneration in models.

This study develops a human neuromuscular junction model from pluripotent stem cells to investigate synaptic dysfunction in familial ALS and assess therapeutic candidates.

This study shows TDP-43 pathology activates immune cells in ALS, linking it to immune dysfunction and suggesting immune monitoring as a diagnostic tool.

The paper shows ALS patient-derived motor neuron networks develop cytopathology and form efficient networks with functional impairments and heightened vulnerability to perturbation.

The paper uses deep learning on images of iPSC-derived motor neurons with fALS mutations to identify disease-relevant phenotypes and molecular differences.