Genetic Neurodegenerative Diseases

Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures

The paper identifies striatum-selective molecular interactions of huntingtin using multi-epitope assays and models, revealing its role in transcriptional regulation and disease mechanisms.

The targeting of non-fibrillar polyQ via distinct VCP-proteasome coupling

This study investigates how VCP and proteasomes degrade non-fibrillar polyQ intermediates in neurodegenerative diseases, revealing a distinct VCP-20S coupling mechanism.

Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease.

This study examines developmental changes in indirect-pathway medium spiny neurons in HD mouse models, finding transient electrophysiological and anatomical alterations that may contribute to disease progression.

Establishment of a second-generation transgenic marmoset model of polyglutamine disease recapitulating neurological symptoms and pathology

This paper describes a second-generation transgenic marmoset model of SCA3 that replicates motor impairments and neuropathology, offering a platform for studying disease mechanisms and therapies.

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

This paper identifies hub genes, miRNAs, and TFs in Huntington's disease using NGS data and bioinformatics analysis, revealing potential molecular markers for diagnosis and treatment.

Allelic Diversity, de novo CAG Expansions, and Intergenerational Instability at the HTT Locus in a clinical sample of Huntingtons Disease from India

The paper analyzes allelic diversity and CAG repeat instability in HD patients from India, finding a strong inverse correlation between repeat length and age at onset, and reporting de novo expansions.

Early alterations of motor learning and corticostriatal network activity in a Huntington's disease mouse model

This study identifies early motor learning deficits and corticostriatal network alterations in a Huntington's disease mouse model before motor symptoms appear.

CellPHIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington's Disease, Including Genetic Modifiers of Neuronal Development and Morphology

The paper integrates pathway discovery with pooled genetic perturbation to identify modifiers of Huntington's disease, revealing genes involved in neuronal development and morphology.

VPS13D mutations disrupt mitochondrial homeostasis and locomotion in Caenorhabditis elegans

This study shows that VPS13D mutations in C. elegans cause mitochondrial dysfunction and locomotion defects, mirroring human SCAR4 disorders.

PYK2 in the dorsal striatum of Huntington disease R6/2 mouse model

This study examines PYK2 levels and effects of its restoration in the striatum of HD mouse models and human patients, finding reduced levels but only partial improvement in motor phenotypes.

Gene Editing for ATXN3 Inactivation in Machado-Joseph disease: CRISPR-Cas9 as a Therapeutic Alternative to TALEN-Induced Toxicity

This study compares CRISPR-Cas9 and TALEN gene editing in a mouse model of Machado-Joseph disease, showing CRISPR-Cas9 reduces ATXN3 aggregates and delays disease progression.

Presymptomatic Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis

The paper investigates presymptomatic manipulation of cortical neuron activity in HD mice to restore E/I balance and slow disease progression.

Sex specific disruptions in Protein Kinase Cγ signaling in a mouse model of Spinocerebellar Ataxia Type 14

The paper develops a mouse model of SCA14 with a clinically relevant PKCγ mutation, identifies sex-specific disease mechanisms, and highlights potential therapeutic targets for males.

Optogenetic restoration of neuron subtype-specific cortical activity ameliorates motor deficits in Huntington's Disease mice

The paper shows optogenetic activation of VIP-INs in HD mice restores motor function by normalizing activity in VIP-INs and CSPNs.

Formation of amyloid-like HTTex1 aggregates in neurons, downregulation of synaptic proteins and early mortality of Huntington's disease flies are causally linked

This study links mHTTex1 aggregation in neurons to synaptic dysfunction and early mortality in HD flies through machine learning analysis and RNAi knockdown experiments.

Insights into Dentatorubral-Pallidoluysian Atrophy from a new Drosophila model of disease

This paper develops a Drosophila model of DRPLA by expressing human ATN1 with normal or pathogenic polyglutamine repeats, showing that pathogenic ATN1 causes toxicity and identifies potential therapeutic targets.

mTOR inhibition in Q175 Huntington's disease model mice facilitates neuronal autophagy and mutant huntingtin clearance

This study shows that mTOR inhibition in HD model mice improves autophagy and reduces mutant huntingtin accumulation.

Huntingtin is essential for synaptic plasticity in the adult hippocampus

This study shows that wild-type huntingtin (wtHTT) is essential for synaptic plasticity in the adult hippocampus, as its loss impairs long-term potentiation and post-tetanic potentiation.

Human striatal progenitor cells that contain inducible safeguards and overexpress BDNF rescue Huntington's disease phenotypes in R6/2 mice

This study shows that human striatal progenitor cells overexpressing BDNF and with inducible safety switches improve HD symptoms in R6/2 mice.

Identification of genetic modifiers of Huntington's disease somatic CAG repeat instability by in vivo CRISPR-Cas9 genome editing

The paper identifies genetic modifiers of Huntington's disease somatic CAG repeat instability using CRISPR-Cas9 in HD knock-in mice, revealing new therapeutic targets.

The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1

The paper introduces the Myotonic Dystrophy Splice Index (SI) as a biomarker that correlates with muscle strength and mobility in DM1 patients.

Intrastriatal delivery of a zinc finger protein targeting the mutant HTT gene by AAV9 obviates lipid phenotypes in brain and plasma of zQ175DN HD mice

The paper shows that reducing mutant HTT with a zinc finger protein in HD mice prevents lipid changes in brain and plasma.

Transcriptomic analysis of repeat expansion-ataxias uncovers distinct non-neuronal cell type-specific signatures of disease across the human brain

This study uses bulk and single nuclear RNA-sequencing to analyze transcriptomic changes in repeat expansion ataxias, revealing distinct non-neuronal cell type-specific disease signatures across the human brain.

Mutant Huntingtin exon1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MSH3 silencing, and aggregation

The paper detects HTT1a protein in Huntington's disease mouse brain using western blot with neo-epitope antibodies and shows that reducing MSH3 lowers HTT1a levels.

The TRX assay for triplet repeat expansions

The paper introduces a new assay called TRX to monitor CAG*CTG triplet repeat expansions more rapidly and sensitively than existing methods.

Altered calcium responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes

This study investigates FXN depletion in cerebellar astrocytes, revealing altered calcium responses and antioxidant properties that may contribute to neurodegeneration in Friedreich's ataxia.

Corticostriatal Maldevelopment in the R6/2 Mouse Model of Juvenile Huntington Disease

This paper examines corticostriatal development in the R6/2 mouse model of juvenile Huntington disease, finding early cortical malformations and transient synaptic deficits that normalize by postnatal day 21.

CRISPR/Cas9-induced double-strand breaks in huntingtin locus lead to CAG repeat contraction through the extensive DNA end resection and homology-mediated repair

This study shows that CRISPR/Cas9-induced DSBs in the huntingtin locus cause CAG repeat contraction through DNA end resection and homology-mediated repair in human cells.

FGF14 repeat length and mosaic interruptions: modifiers of SCA27B?

The paper investigates FGF14 repeat interruptions in ataxia patients and unaffected individuals, finding that mosaic interruptions (mDRILS) correlate with age at onset and affect pathogenicity.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system

This study tracks the progression of pathogenic huntingtin protein aggregates and their physiological impacts in a Drosophila model of Huntington's Disease.