Genetic Neurodegenerative Diseases

Ataxia Telangiectasia triggers deficits in Reelin pathway

The paper identifies reduced Reelin pathway components in Ataxia Telangiectasia, linking them to cerebellar neurodegeneration and suggesting potential therapeutic targets.

N-terminal phosphorylation of Huntingtin: A molecular switch for regulating Htt aggregation, helical conformation, internalization and nuclear targeting.

This study investigates how phosphorylation at S13 and S16 of Httex1 affects its structure, aggregation, and subcellular localization, revealing a phosphorylation-dependent switch that regulates its function.

Transcriptomic Dynamics of a non-coding trinucleotide repeat expansion disorder SCA12 in iPSC derived neuronal cells: signatures of interferon induced response

This study establishes iPSC-derived neuronal cell lines for SCA12, identifies interferon signaling and inflammatory signatures as key transcriptomic features.

Atxn2-CAG100-knock-in affects mouse lifespan and vestibulo-cerebellar function via neural disconnection

This paper describes a novel SCA2 mouse model with CAG100 expansion in Atxn2, showing reduced lifespan and vestibulo-cerebellar dysfunction due to axon-myelin disconnection.

Impairment of neuronal mitophagy by mutant huntingtin

This study shows mutant huntingtin impairs neuronal mitophagy by disrupting key protein interactions and complexes, leading to mitochondrial dysfunction and neurodegeneration in Huntington's disease.

A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease

The paper identifies a human SNP that modifies post-translational myristoylation of huntingtin, altering its proteolysis and contributing to Huntington disease pathogenesis.

Feeding Schedule And Proteolysis Regulate Autophagic Clearance Of Mutant Huntingtin

This study shows that scheduled feeding and prevention of caspase-6 cleavage enhance autophagic clearance of mutant huntingtin in HD models and patients.

Systematic genetic interaction studies identify histone demethylase Utx as potential target for ameliorating Huntington’s disease

The paper identifies Utx as a potential therapeutic target for Huntington’s disease by showing its inhibition rescues HTT-induced pathology in a Drosophila model.

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

This study develops an inducible mouse model of Friedreich’s Ataxia to investigate reversible phenotypes by modulating frataxin levels and observing functional recovery.

Minimizing carry-over PCR contamination in expanded CAG/CTG repeat instability applications

The paper introduces a method to reduce PCR carry-over contamination in expanded CAG/CTG repeat instability studies using Uracil N-Glycosylase and dUTP.

Oxidative stress and loss of Fe-S proteins in Friedreich ataxia induced pluripotent stem cell-derived PSNs can be reversed by restoring FXN expression with a benzamide HDAC inhibitor.

This study shows that FXN deficiency in FRDA patient-derived PSNs can be partially reversed by a benzamide HDAC inhibitor, restoring Fe-S proteins and reducing oxidative stress.

Genetic drivers of repeat expansion disorders localize to 3-D chromatin domain boundaries

The paper identifies that STRs causing repeat expansion disorders are located at 3-D chromatin domain boundaries, which are enriched in CpG islands and may contribute to epigenetic instability.

Reversal of molecular pathology by RNA-targeting Cas9 in a myotonic dystrophy mouse model

RNA-targeting Cas9 reverses molecular pathology in a myotonic dystrophy mouse model by eliminating toxic CUG RNA and restoring normal cellular functions.

Protein Phosphatase 1 Regulates Huntingtin Exon 1 Aggregation And Toxicity

This study shows that protein phosphatase 1 (PP1) regulates huntingtin exon 1 (HTTex1) aggregation and toxicity by modulating phosphorylation at T3.

Tissue-specific downregulation of EDTP suppresses polyglutamine protein aggregates and extends lifespan in Drosophila

This study shows that reducing EDTP in specific Drosophila tissues reduces polyglutamine aggregates and extends lifespan.

Peripheral Htt silencing does not ameliorate central signs of disease in the B6. HttQ111/+ mouse model of Huntington’s Disease

This study shows that reducing huntingtin in peripheral organs of HD mice does not improve central nervous system disease signs.

Evolving Notch polyQ tracts reveal possible solenoid interference elements

The paper identifies conserved polyQ insertion slots in Notch and Huntingtin proteins, suggesting they function as ankyrin repeat interference elements that dynamically compete with solenoid formation.

Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington’s disease

This study shows that B6.HttQ111/+ mice exhibit early transcriptional and proteostatic deficits before synapse loss and neurodegeneration in HD.

Research on Mitochondrial DNA Mutations in Patients with SCA3/MJD

This study investigates mitochondrial DNA mutations in SCA3/MJD patients and finds higher mutation frequency but no significant copy number difference compared to healthy controls.

Genome-scale transcriptional regulatory network models for the mouse and human striatum predict roles for SMAD3 and other transcription factors in Huntington’s disease

The paper builds genome-scale transcriptional regulatory networks for mouse and human striatum, identifying SMAD3 as a key regulator in Huntington’s disease.