Genetic Neurodegenerative Diseases

Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1

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

TALEN-induced contraction of CTG trinucleotide repeats in myotonic dystrophy type 1 cells

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.

Blood DDIT4 and TRIM13 transcript levels mark the early stages of Machado-Joseph disease

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.

Trehalose Consumption Ameliorates Pathogenesis in an Inducible Mouse Model of the Fragile X-associated Tremor/Ataxia Syndrome

This study evaluates the therapeutic potential of trehalose in a mouse model of FXTAS, showing it reduces protein aggregation and improves motor function when administered preventively but not when used as a treatment.

Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model

Regulation of Toxic RNA Foci and Repeat Expansion DMPK Transcripts: Role of MBNL Proteins and RNA Decay Pathways

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.

Bidirectional transcription at the PPP2R2B gene locus in spinocerebellar ataxia type 12

This study identifies bidirectional transcription at the PPP2R2B gene locus in SCA12 and shows that expanded antisense transcripts are toxic and contribute to disease pathogenesis.

Reduced cerebellar Gq-protein signaling elicits early onset spatial navigation deficits in a SCA6 mouse model

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.

Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state

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

Development of a cellular reporter assay to measure activity of MutSβ, a therapeutic target for Huntington's disease

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

Activin A targets extrasynaptic NMDA receptors to improve neuronal and behavioral deficits in a mouse model of Huntington disease

Structural and connectivity parameters reveal compensation patterns in young patients with non-progressive and slow-progressive cerebellar ataxia

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

Endosomal dysfunction contributes to cerebellar deficits in spinocerebellar ataxia type 6

This study identifies endosomal dysfunction in SCA6 mouse models, linking it to impaired BDNF-TrkB signaling and proposing endo-lysosomal targeting as a therapeutic strategy.

Neuroprotective effects of hepatoma-derived growth factor in models of Huntington's disease

This study shows that hepatoma-derived growth factor (HDGF) has neuroprotective effects in Huntington's disease models by reducing mutant Huntingtin toxicity and aggregation.

Phenotypic defects from the expression of wild-type and pathogenic TATA-Binding Proteins in new Drosophila models of Spinocerebellar Ataxia Type 17

This study introduces two new Drosophila models expressing human TBP with polyQ repeats to study SCA17 pathology and its effects on neurodegeneration.

IKBKB reduces huntingtin aggregation by phosphorylating Serine 13 via a non-canonical IKK pathway

The paper shows IKBKB reduces mutant huntingtin aggregation by phosphorylating S13 via a non-canonical IKK pathway.

Drug repurposing of dopaminergic drugs to inhibit Ataxin-3 aggregation

This study identifies dopamine and catecholamines as inhibitors of Atx3 aggregation, suggesting potential use of dopaminergic drugs for MJD treatment.

Length-dependent RNA foci formation and RAN translation are associated with SCA12 disorder

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.

Integrative determination of the atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington's disease

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

Widespread dysregulation of mRNA splicing implicates RNA processing in the development and progression of Huntington's disease

This study identifies splicing dysregulation in RNA processing and neuronal function genes in early and late-stage Huntington's disease using an isogenic neuronal cell model and post-mortem data.

Modulation of Karyopherin Levels Attenuates Mutant Ataxin-1-Induced Neurodegeneration

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

Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington's disease models.

Juvenile and adult expression of polyglutamine expanded huntingtin produce distinct aggregate distributions in Drosophila muscle

This study expresses a pathogenic HD construct in Drosophila muscle and finds distinct aggregate distributions and phenotypes depending on expression timing and level.

Evidence for glutamate excitotoxicity that occurs before the onset of striatal cell loss and motor symptoms in an ovine Huntington's Disease model.

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

Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington disease

Chronic cholesterol delivery via brain-permeable nanoparticles improves cognitive and motor function and reduces mutant Huntingtin aggregates in HD mice.

Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia

The paper develops and validates a strategy to detect FGF14 GAA repeat expansions using PCR and Sanger sequencing, showing comparable accuracy to nanopore sequencing and suitable for clinical use.

Investigation of RFC1 tandem nucleotide repeat locus in diverse neurodegenerative outcomes in an Indian cohort

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

Short Tandem Repeats of Human Genome Are Intrinsically Unstable in Cultured Cells in vivo

The paper investigates STR instability in cultured human cells using sequencing methods and finds STRs are intrinsically unstable during cloning and in cell populations.

Lysine 117 on ataxin-3 modulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3

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.

Large-scale expansions and replication stalling of Friedreich's ataxia GAA repeats in an experimental mammalian system

This study develops an experimental system to analyze GAA repeat expansions and replication fork stalling in human cells, finding that repeat expansions depend on proteins involved in replication fork stalling and restart.