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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.

项目摘要脊髓小脑性共济失调1型（SCA 1）是一种由CAG引起的常染色体显性遗传性神经退行性疾病 ATXN 1中的三核苷酸重复扩增，导致ATXN 1中异常长的多聚谷氨酰胺束。随后的蛋白质，共济失调蛋白-1（ATXN 1）。突变体ATXN 1具有错误折叠的倾向，抵抗细胞降解，毒性也会随着浓度的增加而增加有证据表明，这种毒性是通过一种功能增强机制发生的指出转录紊乱是早期症状前的致病事件。我们最近发现浦肯野细胞（SCA 1中最脆弱的细胞）最早的异常不是由细胞引起的，自主变化，但在非细胞自主的方式通过影响小脑的增殖和命运，产后干细胞在本提案中，我们将检验以下假设，即潜在的SCA 1病理学具有其根源于早期的发展过程，如果这些缺陷被克服，人们可能能够延迟或改善以后的神经变性，从而为治疗这种目前无法治疗的病症铺平了道路。

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.