Amyotrophic Lateral Sclerosis Research

The paper shows that separable interactions in A1-LCD allow tunable metastability of condensates, which can suppress amyloid fibril formation even with ALS mutations.

This study shows that TDP-43 and FUS cytoplasmic inclusions impair DNA damage response and repair, and that pharmacological stimulation of DDR can rescue these defects in ALS models.

This study shows that TDP-43 aggregation in stress granules requires up-concentration and oxidative stress, leading to intra-condensate demixing and pathological aggregates.

The paper investigates how a yeast model of inborn metabolism errors affects TDP-43 aggregation and toxicity, finding that it shifts aggregates toward an amyloid-like state while reducing toxicity.

This study uses single-cell RNA sequencing to identify shared mitochondrial dysfunction in motor neurons across FUS and TARDBP ALS mutations, suggesting common toxic mechanisms.

This study shows that nuclear import defects drive cell cycle dysregulation in neurodegeneration by impairing nuclear import pathways and causing cell cycle re-entry in neurons.

The paper identifies proteomic differences in cerebrospinal fluid between sporadic and familial ALS subtypes using network analysis and validates biomarkers across neurodegenerative diseases.

The paper identifies lipoamide as a small molecule that dissolves stress granules and improves outcomes in ALS models by modulating redox-sensitive proteins.

The paper shows that silencing SOD1 with optimized di-siRNA extends survival and prevents disease progression in ALS mice.

The paper identifies a multi-protein complex in PBMCs as a target for ALS therapeutic assembly modulators, showing altered composition in ALS patients and responsiveness to treatment.

This study identifies genetic risk factors for FTLD-TDP subtypes using whole-genome sequencing and meta-analysis across multiple cohorts.

This study identifies miR-129-5p as a deregulated microRNA in FTD patients, showing its role in astrocyte dysfunction and neurodegeneration.

The paper demonstrates that allele-specific siRNA can effectively silence a dominant SETX mutation in ALS4, restoring R-loop levels in patient cells.

This study shows that reducing GPNMB in progranulin-deficient myeloid cells impairs lysosomal function and immune responses, suggesting GPNMB is essential for maintaining immune homeostasis.

The paper identifies neuronal vulnerability to C9orf72 repeat expansion by analyzing transcriptional states in a Drosophila model, finding that Xbp1 expression correlates with resistance to toxicity.

The paper identifies image biomarkers in SOD1-G93A mouse muscle biopsies that track ALS progression from presymptomatic to advanced stages using computational analysis.

This study shows that FUS-induced splicing changes lead to cytoplasmic accumulation of hnRNP A2b/B1 splice variants, promoting stress granule formation and motor neuron toxicity in a mouse model of ALS.

This study shows that TDP-43 SUMOylation is a stress response that protects neurons, and its disruption is linked to aging and disease.

The paper establishes an ALS hiPSC model showing axonal downregulation of neuromuscular junction proteins and identifies FUS binding to their mRNAs.

This study introduces DANcer, a deep learning classifier that identifies robust ALS molecular subtypes across bulk and single-cell datasets, showing they correlate with clinical features and cellular mechanisms.

The paper identifies cell type-specific molecular changes in the prefrontal cortex of C9orf72 ALS/FTD patients correlated with pTDP-43 levels.

The paper identifies reduced PUFA levels in FTD/ALS models and shows neuronal PUFA supplementation improves survival and reduces neuronal death.

This study shows that TDP-43 pathology in the TDP43-ΔNLS mouse model drives hyperexcitability in spinal motoneurones, with reversible effects upon transgene resuppression.

This study shows that microglial morphology changes before immunophenotype shifts in ALS, driven by TDP-43 aggregation, suggesting morphological changes may trigger immunological responses.

The paper investigates oligogenic risk in ALS using genome sequencing data, finding that multiple rare variants in known ALS genes increase disease risk but not clinical outcomes.

The paper expands the molecular grammar of polar residues and arginine in FUS prion-like domain phase separation and aggregation by showing additional residues contribute to these processes.

This study demonstrates that CRISPR-CasRx reduces C9orf72 repeat RNAs and DPRs in vitro and in vivo, suggesting its therapeutic potential for ALS/FTD.

This study develops a high-fidelity CRISPR-Cas13 system that reduces C9ORF72 repeat RNA expression in a rodent model, decreasing RNA foci and reversing transcriptional deficits without affecting normal C9ORF72 levels.

The paper identifies RNA biomarker signatures in whole blood transcriptomes of MND patients compared to controls, highlighting differentially expressed genes and associated molecular pathways.

This study identifies opposing roles of p38α phosphorylation and arginine methylation in TDP-43 proteinopathy, showing that phosphorylation promotes aggregation while methylation reduces it.