Amyotrophic Lateral Sclerosis Research

The paper shows TDP-43 and RGNEF regulate axon guidance genes through their opposing effects on long-intron processing in neuronal-like cells.

The paper identifies rare somatic mutations in sporadic ALS and FTD cases, suggesting they contribute to disease and widespread neurodegeneration.

This study shows that the TDP-43M337V mutation in microglia alters miRNA release in a sex-specific way, potentially affecting ALS progression.

This study introduces RD-12500, an siRNA conjugate that effectively reduces SOD1 levels and delays disease progression in late-stage SOD1G93A ALS mice.

The paper develops a deep learning platform to screen compounds for ALS treatment using age-relevant human motor neurons and identifies NCB-0846 as a potential therapeutic.

The paper demonstrates that injectable borax-loaded alginate hydrogels improve motor function and survival in SOD1G93A mice by activating the IGF-Akt-mTOR pathway in muscle, reducing atrophy and inflammation.

This study shows that FGF4 reduces ALS astrocyte reactivity but fails to protect motor neurons in a mouse model, while TNF exacerbates astrocyte dysfunction.

This study investigates the function of the ALS risk variant GGNBP2 in Drosophila motor neurons, showing it regulates autophagy and synaptic development.

This study uses an RNA aptamer to detect TDP-43 aggregation and shows that nuclear TDP-43 pathology and STMN-2 cryptic splicing occur before clinical symptoms in ALS.

This study shows that C9ORF72 deficiency in zebrafish causes retinal degeneration, including reduced thickness, gliosis, and neuronal loss, but not spinal cord pathology.

This study identifies early nuclear phenotypes in SOD1-mutated astrocytes derived from ALS patients that precede reactive transformation and may affect astrocyte-MN communication.

This study shows that expressing a RGNEF N-terminal fragment mitigates TDP-43 toxicity in ALS models by reducing aggregation and neurodegeneration.

This study identifies compartment-specific toxic effects of C9ORF72-derived dipeptide repeats (DPRs) in neurodegenerative disease models, revealing two distinct pathogenic mechanisms contributing to ALS and FTD.

The paper shows that glycolic acid and D-lactate restore axonal trafficking and DNA damage response in FUS and SOD1-ALS patient-derived motoneurons.

The paper analyzes ATAC-seq data from iPSC-derived motor neurons of ALS patients and controls to identify disease-specific chromatin accessibility changes and their predictive power for disease progression.

This study shows HDAC6 inhibition with ACY-738 stabilizes microtubules and reduces lower motor neuron degeneration in mSOD1G93A mice, but does not prevent motor function decline.

This study shows that dysregulated actin dynamics and cofilin phosphorylation are linked to TDP-43 pathology in sporadic ALS, suggesting potential therapeutic targets.

This study identifies KCC2 as an early biomarker and therapeutic target for ALS by showing its downregulation in motor neurons and the ability of KCC2-enhancing compounds to delay disease progression.

This study shows that HuD overexpression impairs neuromuscular junctions and induces apoptosis in ALS models, while its knockdown rescues these defects.

The paper performs a multiomic analysis of ALS patients and mouse models to identify sex differences, molecular subclusters, and the MAPK pathway as a therapeutic target.

The paper shows that FUS and TDP-43 interact in mRNA-rich compartments, with FUS enabling TDP-43 to mix and prevent aggregation, and that this interaction is disrupted by pathological mutations.

This study analyzes genetic and clinical data from PLS patients to assess the role of genetic testing and identify potential disease-associated variants.

The paper generates C9orf72 DPR knock-in mice and identifies an extracellular matrix signature in C9ALS/FTD that is conserved across species and protected by TGF-β1 and COL6A1.

Peripheral AAV-mediated delivery of brain-penetrant PGRN rescues TDP-43 pathology, neurodegeneration and motor phenotypes in FTLD-GRN models.

This study uses 7T-MRI and multimodal layer modeling to identify layer-specific pathology in early-stage ALS patients, revealing distinct iron and calcium accumulation patterns and their relationship to demyelination.

This study shows that targeting G2C4 antisense repeat RNA, not G4C2 sense RNA, mitigates TDP-43 dysfunction in C9orf72 ALS/FTD patient neurons, explaining the failure of previous G4C2 ASO clinical trials.

This study identifies a transient protein folding response in early TDP-43 disease that reduces aggregation, with DNAJB5 as a protective factor, and shows proteomic similarities between mouse and human TDP-43 proteinopathies.

This study shows that polystyrene sulfonate (PSS) reduces toxicity of ALS-linked dipeptide repeat proteins in cellular and iPSC-derived motor neuron models.