Genetic Neurodegenerative Diseases

Age-dependent somatic expansion of the ATXN3 CAG repeat in the blood and buccal cell DNA of individuals with spinocerebellar ataxia type 3

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.

Disentangling the neurobiological bases of temporal impulsivity in Huntington's disease

This study investigates temporal impulsivity in Huntington's disease using a Delay Discounting task and diffusion-tensor imaging to identify white matter correlates.

ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice

This study shows that ASO treatment rescues oligodendrocyte dysfunction in SCA3 mice by targeting mutant ATXN3, suggesting potential for glial-targeted therapies in neurodegenerative diseases.

RFC1 repeat expansion analysis from whole genome sequencing data simplifies screening and increases diagnostic rates

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

A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease

This study shows that reducing MSH3 in Huntington's disease mouse models prevents somatic CAG repeat expansion but does not accelerate disease onset, suggesting somatic expansion may not be required for pathogenesis.

Cas9 Nickase-Mediated Contraction of CAG/CTG Repeats in Vivo is Accompanied by Improvements in Huntington's Disease Pathology

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.

Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression

This study identifies small molecules that lower mutant huntingtin levels, improving HD symptoms and delaying disease progression in mice.

Longitudinal study of neurochemical, volumetric and behavioral changes in Q140 & BACHD mouse models of Huntingtons disease

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

Investigating altered limbic reward system in Huntington's Disease: Implications for apathy

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.

Cell Type Specific CAG Repeat Expansions and Toxicity of Mutant Huntingtin in Human Striatum and Cerebellum

The paper investigates CAG repeat expansions and their association with cell death in specific brain regions in Huntington's disease using molecular profiling.

CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs

This study identifies that CAG repeat expansions create new splice acceptor sites, leading to aberrant repeat-containing RNAs that are translated via canonical AUG-initiated mechanisms.

Different Purkinje cell pathologies cause specific patterns of progressive ataxia in mice

This study shows that different Purkinje cell pathologies in mice lead to distinct patterns of progressive gait ataxia, highlighting the importance of pathological mechanisms in disease progression.

Treatment with sodium butyrate induces autophagy resulting in therapeutic benefits for spinocerebellar ataxia type 3

This study shows that sodium butyrate improves symptoms of SCA3 by enhancing autophagy through PKA/AMPK signaling in both cell and zebrafish models.

Selective Vulnerability of Layer 5a Corticostriatal Neurons in Huntington's Disease

The paper identifies layer 5a corticostriatal neurons as selectively vulnerable in Huntington's disease using single nucleus RNA sequencing and shows they have extensive mHTT-CAG expansions.

Mutant HTT protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

The paper shows that mutant HTT levels decrease with CAG repeat expansion, suggesting therapeutic strategies should target HTT1a instead of full-length HTT.

One-to-one Benefit provided by Antioxidants to cultured skin Fibroblasts from Friedreich Ataxia patients

This study examines antioxidant effects on FRDA fibroblasts, finding variable responses that may hinder clinical conclusions.

Long non-coding RNA TUG1 is down-regulated in Friedreich's ataxia.

This study identifies TUG1 as a blood-based biomarker for Friedreich's ataxia, showing its downregulation in patients and correlation with disease severity.

Spinocerebellar ataxia type 2 has multiple ancestral origins

The paper identifies eleven distinct ancestral haplotypes associated with SCA2 in South American populations, including an unexpected haplotype with a G allele at rs695871.

ATXN2 is a target of N-terminal proteolysis

This study investigates whether ATXN2 with expanded polyQ domains is a target for N-terminal proteolysis, finding that both normal and expanded polyQ ATXN2 undergo cleavage, with specific sequences modulating this process.

Base editing strategies to convert CAG to CAA diminish the disease-causing mutation in Huntington's disease

The paper develops base editing strategies to convert CAG to CAA in Huntington's disease, reducing CAG repeat expansion and showing therapeutic potential.

A phenotypically robust model of Spinal and Bulbar Muscular Atrophy in Drosophila

This paper develops a Drosophila model of SBMA by expressing human AR with pathogenic polyQ repeats, showing motor neuron degeneration and aggregation linked to androgen dependence.

Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington's disease

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

Increased FAN1 expression by mRNA-LNP attenuates CAG repeat expansion in Huntington patients' iPSC-derived astrocytes

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

A model for the dynamics of expanded CAG repeat alleles: ATXN2 and ATXN3 as prototypes

The paper develops a mathematical model to simulate the dynamics of CAG repeat expansions in SCA2 and SCA3/MJD, showing how generations pass before alleles are eliminated or fixed.

Highly Potent Peptide Therapeutics To Prevent Protein Aggregation In Huntington s Disease

This study identifies three peptides that inhibit mHtt fibril formation in vitro, offering potential therapeutic leads for Huntington's disease.

Massive contractions of Myotonic Dystrophy Type 2-associated CCTG tetranucleotide repeats occur via double strand break repair with distinct requirements for helicases

This study investigates the molecular mechanisms of CCTG repeat contractions in DM2 using yeast, showing distinct helicase requirements and chromosomal fragility.

m6A RNA modification of mHtt intron 1 regulates the generation of Htt1a in Huntington's Disease

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

Progressive degeneration in a new Drosophila model of Spinocerebellar Ataxia type 7

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

Identification of two novel DnaJ chaperone family proteins as modifiers of Huntingtin aggregates

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

Aberrant splicing in Huntington's disease via disrupted TDP-43 activity accompanied by altered m6A RNA modification.

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.