Genetic Neurodegenerative Diseases

This study investigates how posttranslational modifications affect the membrane interaction and helical structure of the N-terminal fragment of the huntingtin protein.

This study shows autophagosomes preferentially degrade non-fibrillar polyQ aggregates by interacting with p62, while amyloid fibrils evade clearance due to their non-deformable structure.

The paper identifies clofazimine as a drug that reduces polyQ toxicity by activating PPARγ, improving mitochondrial function in models of polyQ diseases.

This study shows splice modulators like branaplam reduce HTT CAG repeat expansion by affecting PMS1 expression, suggesting PMS1 as a new therapeutic target for Huntington's disease.

This study shows that BDNF and TRiC-inspired reagents can rescue synaptic deficits in HD mouse models.

This study shows that mutant huntingtin aggregates impair glial phagocytosis and phagolysosomal function in Drosophila, leading to prion-like propagation of aggregates and neurodegeneration.

This study examines polysomal architecture changes in a mouse model of Huntington's disease, finding compacted polysomes and increased expression of ribosome stalling relief factors.

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

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.

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.

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

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

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.

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.

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

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.

The paper shows that combining chloride and calcium channel dysfunction in mice worsens myotonic dystrophy symptoms, and calcium blockers can improve survival and function.

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

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

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

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

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.

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

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.

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.

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

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

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.