Amyotrophic Lateral Sclerosis Research

The paper identifies an alternative open reading frame (altORF) within the FUS gene that contributes to toxicity in neurodegenerative models.

This study shows that ENGRAILED-1 promotes motoneuron survival and motor function by preventing denervation and neuronal death.

This study shows that Cx43 hemichannels in astrocytes contribute to ALS progression and that blocking them can protect neurons and improve survival in ALS models.

The paper tests antibody and immune-complex responses to neurofilaments and dipeptide-repeats as biomarkers for ALS progression and stratification.

The paper identifies POM121 as a critical nucleoporin affected by C9orf72 repeat RNA, leading to nuclear pore complex disassembly and neuronal toxicity in ALS/FTD.

The paper characterizes transcriptional changes in ALS motor cortex, identifying microglial activation and synapse-related pathway alterations as key features.

The paper shows that removing mutant SOD1G37R from corticofugal projection neurons prevents their degeneration but does not affect ALS onset or progression.

This study shows that removing subcerebral projection neurons in ALS mice delays disease onset and improves survival, supporting the corticofugal hypothesis of ALS.

This study shows that PR poly-dipeptides from C9orf72 repeat expansion bind Kapβ2 and disrupt FUS droplet melting, contributing to nucleocytoplasmic transport deficits in ALS.

This study uses C. elegans knock-in models to show that autophagy dysfunction contributes to neuronal defects in FUS-related ALS, independent of SQSTM1/p62 function.

The paper identifies a novel retrograde death signal mechanism in ALS motor neurons involving CRMP4-dynein complex formation triggered by muscle-secreted Sema3A.

The paper shows that CHCHD10S59L causes mitochondrial toxicity in Drosophila and HeLa cells, which can be mitigated by inhibiting TDP-43 mitochondrial translocation or PINK1 kinase activity.

This study shows TDP-43 promotes neuromuscular synapse formation in Drosophila by regulating Disc-large expression, with similar mechanisms observed in human ALS tissues.

This study creates a Drosophila model expressing codon-optimized human TDP-43, showing neurodegenerative phenotypes and toxic protein aggregation.

This study shows that inhibiting PIKFYVE kinase rescues both gain- and loss-of-function C9ORF72 disease mechanisms in mouse models of ALS/FTD.

This study identifies a differential lipidomic signature in nuclei of ALS patients, linking lipid changes to disease mechanisms.

This study identifies how ALS-causative FUS mutations disrupt RNA processing and autoregulation, with implications for broader ALS genetic interactions.

The paper identifies early RNA metabolism and splicing alterations in corticospinal neurons in an ALS mouse model, suggesting shared mechanisms across ALS-related genes.

The paper uses a yeast model to analyze multi-omic data from OPTN overexpression, finding distinct genetic and metabolic responses to different ALS-linked genes.

The paper identifies a subclass of sporadic ALS patients with metabolic defects in trans-sulfuration, characterized by increased cysteine and glutathione synthesis and distinct metabolic responses.

The paper investigates FUS mislocalization in ALS, finding it occurs in both VCP-mutation related and sporadic ALS, and links it to aberrant intron retention in SFPQ transcripts.

This study identifies genetic variants and networks associated with ALS using GWAS data, revealing novel loci and functional sub-networks linked to disease.

The paper identifies TP73 variants as risk factors for ALS through exome sequencing and functional assays in cell lines and zebrafish.

The paper shows that cranial nerve motor nuclei innervating eye muscles are spared in a mouse model of SOD1-linked ALS, mirroring human ALS patterns.

The paper identifies a distinct metabolomic subtype in sporadic ALS patients through metabolite profiling and multi-omics integration, showing increased cysteine metabolism and potential therapeutic targets.

This study identifies PTK2 as a suppressor of TDP-43-induced neurotoxicity by regulating p62 phosphorylation and UPS impairment in neuronal cells.

The paper introduces OptoGranules, a light-inducible system to control stress granule dynamics in cells, showing that persistent stress granule assembly leads to ALS-FTD-like pathology.