Amyotrophic Lateral Sclerosis Research

This study creates a lifespan snRNA-seq atlas of mouse spinal cord, revealing how aging and SOD1-G93A ALS interact regionally and cell-type specifically.

The paper develops a zebrafish C9orf72 knockout model for ALS, identifies pizotifen malate as a potential therapeutic, and validates its efficacy in both zebrafish and C. elegans models.

This study identifies LINC00205 as a critical lncRNA that promotes the formation of pathological stress granules in ALS by acting as a scaffold to recruit specific mRNAs and proteins.

This study shows that full-length TDP-43 spreads from the brain to muscle in rats, causing pathology and dysfunction.

This study shows HSV infection increases ALS risk and promotes TDP-43 pathology through ICP0-mediated disruption of PML bodies.

This study shows that early hyperexcitability in ALS patient-derived motor neurons drives mitochondrial hypermetabolism, which later leads to mitochondrial failure and neuron loss.

The paper shows granulin deficiency leads to lysosomal buildup of a TMEM106B C-terminal fragment, explaining how TMEM106B alleles influence FTD risk.

This study shows ANXA11 forms prion-like amyloid fibrils through phase separation, which propagate between cells, induce TDP-43 pathology, and disrupt nucleocytoplasmic transport, linking ANXA11 dysfunction to ALS/FTD.

This study investigates how interactions between RNA and the prion-like domain of hnRNPA1 influence aggregate morphology and infectivity in neurodegenerative diseases.

This study shows that riluzole increases motoneuron excitability in ALS mice due to hyperactive homeostasis, which counteracts the drug's intended effects.

This study presents the first crystal structure of the Ubiquilin Sti1 domain bound to a transmembrane domain, showing that ALS mutations disrupt their interaction and reveal internal placeholder sequences that regulate phase separation.

This paper identifies distinct metabolic signatures in ALS subtypes defined by ferritin and TDP-43 pathology, supporting stratified therapeutic approaches.

The paper identifies a chemical inducer of ribophagy, SALSa, that reduces toxicity of ALS-related arginine-rich peptides and extends lifespan in a Drosophila model.

This study identifies Aldh3a1's role in protecting muscles from ALS progression by detoxifying reactive aldehydes, showing differential expression and functional importance across muscle types.

This study shows that Pml loss worsens NEK1-linked ALS, while Pml induction reduces disease symptoms by clearing Nek1t aggregates.

This study shows that β-adrenergic receptors regulate spinal motoneuron excitability through homeostatic feedback in both wild-type and presymptomatic SOD1 mice.

This study shows ropinirole hydrochloride reduces oxidative stress and neuroinflammation in TDP-43 mutant microglial-like cells by modulating the PI3K-mTOR pathway.

This study shows that fructose-2,6-bisphosphate (F2,6BP) restores genome repair and motor function in TDP-43 pathology-driven motor neuron diseases.

This study shows TDP-43 amyloid forms only when its C-terminal domain arrests in soluble clusters, and this process can be inhibited by co-expressing an oligomeric binder.

This study shows that TDP-43 and FUS are recruited by the R1810me2s-SMN pathway, and their defects affect RNAPII termination and R-loop accumulation, contributing to neurodegenerative disorders.

The paper identifies Fos as a regulator of age-dependent neuroinflammation in a Drosophila model of ALS8, showing its role in modulating inflammation and motor function.

This study identifies cGAS as a key mediator of TDP-43 pathology in ALS and shows that its inhibition reduces RNA splicing defects and neurodegeneration.

The paper develops new single molecule imaging techniques to study how C9ORF72-linked poly(glycine-arginine) peptides disrupt nuclear pore transport and structure, linking these changes to early TDP-43 pathology in ALS/FTD.

This study introduces β-sheet breaking proline residues into FUS prion-like domain to prevent aggregation and toxicity while preserving phase separation and function.

The paper shows that cell-cycle re-entry in motor neurons correlates with distinct ALS outcomes and identifies CDK4/6 inhibition as a potential neuroprotective strategy.

This study identifies a molecular pathway involving TRIM32, UBQLN2, and p62 that forms condensates promoting TDP-43 aggregation in neurodegenerative diseases.

This study shows that C9orf72 repeat expansions alter chromatin loops in neurons, linking RNA-DNA interactions to gene dysregulation in ALS.

The paper investigates how toxic SOD1 oligomers affect extracellular vesicle release pathways in ALS, identifying key proteins and pathways involved.

This study shows HSPB8 interacts with TDP43's low complexity domain to delay fibril formation without affecting elongation rates.

This study identifies an APOE ε4-associated systemic immune proteomic signature in ALS that predicts disease progression independently of clinical features.