Genetic Neurodegenerative Diseases

The paper examines transcriptional changes in striatal neurons in Huntington's disease, finding that striosomal SPNs are most depleted and compartmental markers are dysregulated in both mouse models and human HD.

The paper identifies SNORD13 as a circulating biomarker for Huntington's disease, showing higher levels in HD patients compared to controls and correlating with disease status.

This study examines altered cortical processing of sensory input in Huntington disease mouse models, finding increased LFP power and sensory signal spread in HD mice.

The paper analyzes somatic instability of the CCCTCT repeat in XDP and finds repeat length-dependent expansion in brain regions, with regional patterns and similarities to HTT CAG repeat instability.

The paper identifies FAN1 nuclease activity as a modifier of CAG expansion and age at onset in Huntington's disease through exome sequencing and functional validation.

This study shows Rhes moves between neurons and transports mutant huntingtin in the brain, with Rhes deletion reducing this transport.

This study develops a programmable nanopore sequencing assay for diagnosing all known pathogenic STRs in a single test, accurately diagnosing 27 patients with neurogenetic disorders.

The paper identifies regional transcriptional and physiological differences in Purkinje cells of the cerebellum in SCA1 mice, showing reduced heterogeneity and increased vulnerability in the posterior cerebellum.

The paper introduces a method for accurately estimating GAA repeats in Friedreich ataxia using long-read targeted sequencing, achieving high coverage and throughput.

This study shows that activating the JAK2-STAT3 pathway in astrocytes reduces mutant Huntingtin aggregates and improves disease outcomes in Huntington's disease models.

This study shows endurance exercise reduces motor dysfunction and extends lifespan in Drosophila models of SCA2 and SCA6, but not SCA3, through mechanisms involving Sestrin and autophagy.

This study shows that Huntington's Disease leads to increased release of mitochondrial components via extracellular vesicles due to mitochondrial and lysosomal dysfunction.

The paper analyzes RNA-seq and proteomics data from Huntington disease mouse models to identify disease-specific signatures in the striatum and liver, revealing gender effects and improved proteomics analysis methods.

The paper identifies small molecules that restore mutant Huntingtin conformational flexibility in patient-derived cells using a TR-FRET assay.

This study develops a CRISPR-Cas13d system targeting CAG-expanded HTT RNA in HD models, reducing mutant mRNA and reversing disease phenotypes without significant off-target effects.

This study shows that hypothalamic expression of mutant HTT causes sex-specific metabolic imbalance, and IKKβ inhibition reduces obesity in female HD mice.

This study identifies impaired oligodendrocyte maturation as an early feature in SCA3 disease pathogenesis through longitudinal transcriptomic analysis and functional validation in mice.

This paper describes the creation of a novel HD mouse model, BAC226Q, which accurately recapitulates age-dependent and progressive HD-like phenotypes.

This study characterizes the motoric phenotype of CYP2C19 transgenic mice and finds reduced cerebellar volume and impaired motor function, suggesting a model for cerebellar ataxia.

The paper identifies and validates small-molecule inhibitors of TRMT2A that reduce polyQ aggregation and cell death in human cells.

This study shows that transposable element activation contributes to neurodegeneration in a Drosophila Huntington's disease model and can be inhibited to rescue neurodegeneration and extend lifespan.

The paper shows that CAG repeat expansion in Huntington's disease disrupts splicing, reducing circular RNA production and affecting neural progenitors and striatum before symptoms appear.

The paper identifies Etidronate, an FDA-approved drug, as a method to lower ataxin-2 levels in neurons using a CRISPR screen and validates its efficacy in mice.

This study shows disrupting ATXN1 nuclear localization in a SCA1 mouse model reduces disease-like phenotypes and alters region-specific transcriptomic profiles.

This study shows that nucleolar stress affects mutant Huntingtin toxicity and progression in Huntington disease by altering rRNA maturation and NPM1 localization.

This study shows that microglia and complement proteins drive early synapse loss and cognitive deficits in Huntington's disease by eliminating corticostriatal synapses, and that targeting this pathway can prevent these effects.

The paper shows FAN1 nuclease processes and pauses on slipped-DNA repeats, reducing repeat expansions and delaying disease onset.

The paper examines changes in astrocyte subtypes in HD mouse models, finding increased GFAP+ astrocyte density and clustering in specific striatal regions.

The paper examines the biochemical composition, interactome, and ultrastructural properties of nuclear and cytoplasmic Htt inclusions in mammalian cells and neurons.

This study shows SorCS2 deficiency worsens Huntington's disease in mice by disrupting BDNF signaling and NMDA receptor function in striatal neurons.