A5000555998- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Muscle Physiology and Disorders
Max Delbrück Center
2018-2022
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2018
Abstract Huntington’s disease is caused by the expansion of a CAG repeat within exon 1 HTT gene, which unstable, leading to further expansion, extent brain region and peripheral tissue specific. The identification DNA repair genes as genetic modifiers disease, that were known abrogate somatic instability in mouse models, demonstrated central pathogenesis, threshold for pathogenesis specific cells might not be known. We have previously shown gene incompletely spliced generating small...
Abstract Huntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention Huntington’s disease. When the cytosine, adenine and guanine repeat is expanded, pre-mRNA alternatively processed to generate full-length HTT1a transcripts. encodes aggregation-prone highly pathogenic exon 1 protein. In evaluating huntingtin-lowering approaches, understanding how targeting strategy modulates levels of both transcripts protein isoforms they encode will be...
Amyloidogenic mutant huntingtin exon-1 (mHTTex1) protein aggregates with pathogenic polyglutamine (polyQ) tracts are the potential root cause of Huntington's disease (HD). Here, we assessed gain-of-function toxicity mHTTex1 aggregation in neurons HD transgenic flies. We show that rate and early mortality flies correlated. observed sequestration key synaptic proteins into amyloid-like a concomitant decrease their transcript levels, suggesting progressive aggregate stress leads to an...
The deposition of mutant huntingtin (mHTT) protein aggregates in neurons patients is a pathological hallmark Huntington’s disease (HD). Previous investigations cell-free and cell-based models showed mHTT exon-1 (mHTTex1) fragments with pathogenic polyglutamine (polyQ) tracts (>40 glutamines) to self-assemble into highly stable, β-sheet-rich fibrillar morphology. HD knock-in mouse have not been extensively studied regard aggregation. They endogenously produce full-length polyQ tract as...