Genetic Neurodegenerative Diseases

The paper identifies molecular signatures of inflammation, energy metabolism, and vesicle biology in peripheral tissues of Huntington disease patients, suggesting their potential as biomarkers for clinical trials.

The paper develops an amplification-free long-read sequencing method using CRISPR/Cas9 to accurately measure CTG repeat expansions in DM1 patients, identifying a CCG-enriched expanded allele.

This study shows that activation of young LINE-1 elements in the cerebellum causes ataxia by inducing DNA damage, inflammation, and neuronal dysfunction in mice.

The paper identifies a tandem hexamer repeat in TCERG1 that modifies age at motor onset in Huntington's disease, explaining the effect of a previously associated SNP.

This study characterizes full-length CNBP repeat expansions in DM2 patients using Cas9-mediated nanopore sequencing, revealing novel repeat patterns and mosaicism.

This study investigates mitochondrial dysfunction and redox changes in early Huntington disease stages using human and mouse models, showing increased mitochondrial activity and altered morphology.

This study investigates miRNA biogenesis defects in HD brain tissue, finding downregulation of key enzymes and maturation defects, primarily in the striatum.

This study shows that in a mouse model of SCA3, abnormal cerebellar output occurs early, before visible neuronal damage, and may be a target for therapy.

This study shows that reducing CK2 in HD mice improves neuroinflammation, HTT aggregation, and motor deficits by reducing synucleinopathy.

This study shows that gut bacteria influence Huntington's disease progression in Drosophila models, with antibiotics and compounds like crocin reducing disease symptoms while E. coli worsens them.

This study investigates retinal structure and function in SCA3 patients and transgenic mice, finding correlations between retinal changes and disease severity.

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.

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.

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

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.

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

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

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

This paper describes a novel mouse model of Ataxia Telangiectasia with a nonsense mutation in Atm, showing ataxia, cerebellar defects, and potential therapeutic response to SMRT compounds.