A5057133330- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- DNA Repair Mechanisms
- Botulinum Toxin and Related Neurological Disorders
- Traumatic Brain Injury Research
- Electromagnetic Fields and Biological Effects
- Muscle Physiology and Disorders
- Functional Brain Connectivity Studies
University of Minnesota
2020-2024
Massachusetts General Hospital
2023
University of Minnesota System
2022
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited caused by expansion of translated CAG repeat encoding glutamine tract in the ataxin-1 (ATXN1) protein. Despite advances understanding pathogenesis SCA1, there are still no therapies to alter its progressive fatal course. RNA-targeting approaches have improved disease symptoms preclinical rodent models several neurological diseases. Here, we investigated therapeutic capability an antisense oligonucleotide (ASO) targeting mouse...
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced phenotypes, we developed floxed conditional knockin mouse (f-ATXN1146Q/2Q) with Atxn1 coding exons replaced human ATXN1 encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor cognitive deficits, wasting,...
Purpose The primary goal of this study was to investigate whether chronic exposures ultra‐high B 0 fields can induce long‐term cognitive, behavioral, or biological changes in C57BL/6 mice. Methods mice were chronically exposed 10.5‐T 16.4‐T magnetic (3‐h exposures, two exposure sessions per week, 4 8 weeks exposure). In vivo single‐voxel 1 H resonance spectroscopy used possible neurochemical the hippocampus. addition, a battery behavioral tests, including Morris water‐maze, balance‐beam,...
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of basal ganglia. Transcriptional perturbations synaptic genes neuroinflammation key processes that precede MSN dysfunction motor symptom onset. Understanding interplay between these crucial to develop effective therapeutic...
Spinocerebellar ataxia type 1 (SCA1) is a lethal, autosomal dominant neurodegenerative disease caused by polyglutamine expansion in the ATAXIN-1 (ATXN1) protein. Preclinical studies demonstrate therapeutic efficacy of approaches that target and reduce Atxn1 expression non-allele-specific manner. However, using Atxn1−/− mice raise cautionary notes reductions ATXN1 might lead to undesirable effects such as reduction activity tumor suppressor Capicua (CIC), activation protease β-secretase...
ABSTRACT Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ATXN1 protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced phenotypes, we developed floxed conditional knockout mouse model ( f-ATXN1 146Q/2Q ) having Atxn1 coding exons replaced human encoding 146 glutamines. F-ATXN1 mice manifest SCA1-like phenotypes including motor cognitive deficits, wasting, decreased...
Abstract Background Huntington’s Disease (HD) is a neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. This mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of basal ganglia. Transcriptional perturbations synaptic genes neuroinflammation key processes that precede MSN dysfunction motor symptom onset. Understanding interplay between these crucial to develop...
SUMMARY Spinocerebellar ataxia type 1 (SCA1) is a dominant trinucleotide repeat neurodegenerative disease characterized by motor dysfunction, cognitive impairment, and premature death. Degeneration of cerebellar Purkinje cells frequent prominent pathological feature SCA1. We previously showed that transport ATXN1 to cell nuclei required for pathology, where mutant alters transcription. To examine the role nuclear localization broadly in SCA1-like pathogenesis, CRISPR-Cas9 was used develop...