Amyotrophic Lateral Sclerosis Research

This study shows that astrocytic expression of mutant FUS causes TNF-dependent neurodegeneration in ALS, highlighting a therapeutic target.

This study shows that reducing tau with a degrader prevents mitochondrial fragmentation and oxidative stress in ALS models.

The paper identifies SF2/SRSF1 as a suppressor of TDP-43 toxicity in both neurons and glia through a Drosophila behavioral screen.

The paper identifies MFN2 mutations in ALS patients and shows they impair mitochondrial function and increase TDP-43 levels in zebrafish models.

The paper identifies miR-181 as a prognostic biomarker in ALS, showing it predicts higher mortality risk and improves prognosis prediction when combined with NfL.

This study shows that loss of C9orf72 disrupts the Ran-GTPase gradient and creates diverse cytoplasmic Importin β-1 granules in neurons, linking it to nucleocytoplasmic transport defects.

This study uses C. elegans models to show that eIF2D is essential for RAN translation in C9orf72 expansions, and its inhibition extends lifespan and reduces disease.

This study shows that TBK1 deficiency in human motor neurons causes TDP-43 proteinopathy through lysosomal dysfunction, and restoring TBK1 rescues the pathology.

This study shows poly-GA DPRs are taken up by astrocytes via endocytosis, spread to motor neurons, and cause axonal swellings through lysosomal dysfunction.

The paper identifies ELAVL3 as a downregulated RNA binding protein in ALS, showing nuclear depletion and mislocalization in motor neurons, with findings suggesting loss of function rather than cytoplasmic toxicity.

This study identifies CHMP2B as a regulator of TDP-43 phosphorylation and proteotoxicity through CK1 turnover, independent of autophagy-lysosomal pathways in neurodegenerative diseases.

This study uses image-based deep learning to uncover novel morphological changes in VCP-mutant human motor neurons under stress, revealing disease-relevant information from fluorescent markers.

This paper identifies SPOP as a conserved regulator of C9orf72 dipeptide toxicity in C. elegans and mammalian neurons, showing SPOP inhibition protects against toxicity.

The paper investigates leptin signaling alterations in ALS by analyzing mRNA, protein expression, and plasma levels in TDP-43A315T mice compared to WT controls.

The paper shows that age-related DNA demethylation in the TARDBP 3'UTR reduces alternative splicing and increases TARDBP mRNA expression in the human motor cortex, linking this to earlier ALS onset.

This study shows that TDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila brains, and that modulating GABA neurotransmission can reverse locomotion defects in TDP-43-deficient flies.

This study shows that defective cyclophilin A (PPIA) leads to TDP-43 proteinopathy, contributing to ALS and FTD by disrupting TDP-43 function and causing neurodegeneration.

This study shows that wild-type FUS rescues ALS-like disease caused by mutant FUS by activating an autoregulatory loop that reduces cytoplasmic mutant FUS levels.

This study introduces a streamlined CRISPR workflow to generate isogenic iPSCs with specific ALS-related mutations for modeling the disease.

This study shows PDI protects neuronal cells from DNA damage caused by etoposide, H2O2, or mutant TDP-43, and localizes to DNA damage sites in the nucleus.

The paper examines whether blood-spinal cord barrier breakdown correlates with motor neuron loss and TDP-43 proteinopathy in ALS, finding they have distinct regional patterns.

The paper establishes a yeast model of Matrin3, showing it forms inclusions and is toxic, and identifies Hsp90 and Sti1 as modifiers of its misfolding and toxicity.

The paper identifies NUP50 gene variants and reduced expression as risk factors for ALS through transcriptome-wide association and functional studies.

The paper identifies metabolic reprogramming in neurons of familial ALS models, showing impaired glycolytic flux with maintained citric acid cycle activity and normal ATP levels.

This study shows riluzole does not improve disease outcomes in a mouse model of ALS with cytoplasmic TDP-43 pathology.

This study shows that cortical hyperexcitability in mice leads to ALS-like motor symptoms and pathology through a dying-forward mechanism.

This study shows that inhibiting SRSF1-dependent nuclear export of C9ORF72-repeat transcripts in ALS models protects neurons and identifies key RNA changes involved in disease.

The paper was withdrawn due to lack of full author consent and is not intended for citation.

The paper uses molecular dynamics simulation and machine learning to analyze disease-associated mutations in TDP-43 and identifies structural features linked to protein stability and pathogenesis.

This paper develops an automated method to quantify TDP-43 and FUS mislocalization in human cell lines to assess the pathogenicity of FTD and ALS gene variants.