Equipment Supplement: Understanding the Cellular Basis of Movement Disorders

设备补充：了解运动障碍的细胞基础

基本信息

批准号：
10755946
负责人：
Puneet Opal
金额：
$ 1.86万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10755946
关键词：
Ablation Adult Affect Agonist Alzheimer&apos s Disease Astrocytes Ataxia Autopsy Behavior assessment Brain CAG repeat Cannabinoids Cells Cerebellar Cortex Cerebellar degeneration Cerebellum Data Defect Development Developmental Process Disease Disease Progression Electrophysiology (science)Equipment Event Functional disorder Genetic Genetic Transcription Human Huntington Disease Impairment Interneurons Life Modeling Movement Disorders Mus Myoepithelial cell Nerve Degeneration Neurodegenerative Disorders Neurons Neurotransmitters Parkinson Disease Pathogenicity Pathologic Pathology Patients Phenotype Play Population Process Proliferating Proteins Purkinje Cells Resistance Role Seizures Sonic Hedgehog Pathway Stimulation of Cell Proliferation System Testing Therapeutic Time Toxic effect Trinucleotide Repeat Expansion Type 1 Spinocerebellar Ataxia Wild Type Mouse ataxin-1 autosome behavior test cyclopamine endogenous cannabinoid system experimental study gain of function gamma-Aminobutyric Acid inhibitor knock-down mutant network dysfunction neuroprotection overexpression pharmacologic polyglutamine postnatal preclinical trial presynaptic prevent receptor sonic hedgehog receptor stellate cell stem cell niche stem cell population stem cells therapeutic target transcriptomics transmission process

项目摘要

Project Summary Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide repeat expansion in ATXN1 that leads to an abnormally long polyglutamine tract in the subsequent protein, ataxin-1 (ATXN1). Mutant ATXN1 has a propensity to misfold, resist cellular degradation, and increase in toxicity as its levels rise. This toxicity occurs by a gain of function mechanism with evidence point to transcriptional derangements as an early, presymptomatic pathogenic event. We recently discovered that the earliest abnormalities in Purkinje cells (cells that are most vulnerable in SCA1) are not caused by cell- autonomous changes but in a non-cell autonomous manner by affecting the proliferation and fate of cerebellar post-natal stem cells. In this proposal, we will test the hypothesis that the underlying SCA1 pathology has its roots in early developmental processes and that if these defects are overcome one might be able to delay or ameliorate later neurodegeneration, thus paving the way for therapy for this currently untreatable condition.

项目摘要 1型脊髓脑性共济失调（SCA1）是由CAG引起的常染色体显性神经退行性疾病三核苷酸重复膨胀在ATXN1中导致异常长的聚谷氨酰胺道随后的蛋白质，共生1（ATXN1）。突变ATXN1具有错误折叠的倾向，抵抗细胞降解，并随着其水平上升而增加毒性。这种毒性是通过获得证据的功能机制而发生的指向转录毁灭作为早期的，症状的病原事件。我们最近发现浦肯野细胞中最早的异常（SCA1中最脆弱的细胞）不是由细胞引起的自主变化，但通过影响小脑的增殖和命运，以非细胞自主的方式产后干细胞。在该提议中，我们将检验以下假设，即潜在的SCA1病理具有根源在早期发展过程中，如果克服这些缺陷，可能会延迟或改善后来的神经退行性，从而为这种目前不可治疗的疾病铺平了治疗的道路。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An investigation of diffusion imaging techniques in the evaluation of spinocerebellar ataxia and multisystem atrophy.

DOI：
10.1016/j.jocn.2014.08.006
发表时间：
2015-01
期刊：
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
影响因子：
0
作者：
Rozenfeld MN;Nemeth AJ;Walker MT;Mohan P;Wang X;Parrish TB;Opal P
通讯作者：
Opal P

The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP.