Genetic Neurodegenerative Diseases

This study shows that reduced RARβ signaling in HD mouse models accelerates motor and transcriptional abnormalities, suggesting a protective role for RARβ in disease progression.

The paper quantifies age-related somatic expansion of the ATXN3 CAG repeat in blood and buccal cells of SCA3 patients, revealing strong age associations and genetic polymorphism effects.

The paper develops a whole genome sequencing method to detect RFC1 repeat expansions, improving diagnostic rates and simplifying the workflow for cerebellar ataxia diagnosis.

The paper demonstrates that CRISPR-Cas9 nickase can contract CAG/CTG repeats in patient-derived cells and improve molecular and behavioral phenotypes in Huntington's disease.

This study examines neurochemical, volumetric, and behavioral changes in HD mouse models using MRI and MRS to identify early biomarkers of disease progression.

This study investigates reward processing deficits in Huntington's Disease using fMRI, finding reduced activity in the left ventral striatum in apathetic patients, suggesting reward insensitivity contributes to apathy.

This study investigates how MutSβ binds to long extruded DNA trinucleotide repeats and identifies compounds that block this interaction without affecting mismatched DNA.

This study shows that reducing MMR gene expression in HD iPSCs slows CAG repeat expansion, suggesting these genes as therapeutic targets for HD.

The paper shows that increasing FAN1 expression in HD patient astrocytes reduces CAG repeat expansion using mRNA-LNP.

This study investigates how m6A RNA modifications in Htt intron 1 regulate the production of the pathogenic Htt1a transcript in Huntington's Disease.

This paper develops new Drosophila models of SCA7 with polyQ repeats, showing age- and repeat-length-dependent neurodegeneration and protein aggregation.

The paper identifies two DnaJ chaperone proteins, CG5001 and P58IPK, that reduce HTT aggregation in HD models, suggesting their potential as therapeutic targets.

This study identifies TDP-43 dysfunction and reduced m6A modification as mechanisms causing aberrant splicing in Huntington's disease using mouse and human brain data.

This study identifies increased intrinsic membrane excitability in SCA1-KI mice as a novel mechanism underlying hypertrophic olivary degeneration without inhibitory denervation.

This study uses TALENs to contract CTG repeats in DM1 cells, achieving 68% contraction with a recoded TALEN, while SaCas9 failed, and identifies potential off-target effects.

This study identifies blood transcript levels of DDIT4 and TRIM13 as potential biomarkers for early-stage Machado-Joseph disease, showing high accuracy in distinguishing carriers from controls.

This study investigates how MBNL proteins and RNA decay pathways regulate mutant DMPK mRNA in DM1, showing that their absence reduces RNA foci and promotes mRNA degradation.

This study shows that SCA6 mice exhibit early cognitive deficits in spatial navigation linked to reduced Gq-protein signaling in the cerebellum, preceding motor impairments.

This study uses multi-omic analysis to identify a neuroprotective astrocyte state in Huntington disease that correlates with delayed disease onset and neuroprotection.

The paper develops a cellular reporter assay to measure MutSβ activity and shows its modulation by MSH3 levels and HDAC3 inhibitors.

The paper compares structural and connectivity parameters between non-progressive and slow-progressive cerebellar ataxia patients to identify compensation patterns in motor behavior.

This study identifies molecular signatures of SCA12 by analyzing patient-derived neuronal cell lines and shows CAG repeat expansion leads to RNA foci and RAN translation.

The paper determines the atomic structure of mutant huntingtin exon 1 fibrils using integrative analysis and molecular dynamics simulations combined with experimental data.

This study shows that increasing KPNA levels reduces mutant Ataxin-1-induced neurodegeneration by retaining it in the cytoplasm and decreasing its nuclear accumulation.

The paper identifies transcriptional upregulation of glutamate receptors and downregulation of oxidative phosphorylation in an ovine HD model before neuronal loss and motor symptoms.

The paper investigates the prevalence and association of RFC1 tandem nucleotide repeat expansions with neurodegenerative diseases in an Indian cohort.

This study investigates the role of lysine 117 ubiquitination in modulating toxicity of pathogenic Atxn3 in Drosophila models of SCA3, finding that mutating K117 mildly enhances toxicity and aggregation.

This study shows that altered calcium signaling in Bergmann glia contributes to the electrophysiological changes in Purkinje cells in SCA1 mice, suggesting a therapeutic target for treatment.

The paper combines computational and experimental methods to identify CNG repeat loci potentially linked to spinocerebellar ataxias, finding polymorphic patterns and expression in brain-related genes.