scholarly journals Childhood-Onset Spinocerebellar Ataxia 3: Tongue Dystonia as an Early Manifestation

2019 ◽  
Vol 9 (0) ◽  
Author(s):  
Nester Mitchell ◽  
Gaynel A. LaTouche ◽  
Beverly Nelson ◽  
Karla P. Figueroa ◽  
Ruth H. Walker ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Childhood Onset ◽  
Spinocerebellar Ataxia 3 ◽  
Early Manifestation

Unusual nocturnal motor restlessness in a patient with spinocerebellar ataxia 3

2005 ◽  
Vol 20 (7) ◽  
pp. 899-901 ◽  
Author(s):  
Imad Ghorayeb ◽  
Federica Provini ◽  
Bernard Bioulac ◽  
François Tison
Keyword(s):  
Spinocerebellar Ataxia ◽  
Motor Restlessness ◽  
Spinocerebellar Ataxia 3

Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation

2007 ◽  
Vol 22 (2) ◽  
pp. 251-253 ◽  
Author(s):  
Melissa J. Nirenberg ◽  
Jenny Libien ◽  
Jean-Paul Vonsattel ◽  
Stanley Fahn
Keyword(s):  
Multiple System Atrophy ◽  
Gene Mutation ◽  
Spinocerebellar Ataxia ◽  
Spinocerebellar Ataxia 3

Spinocerebellar ataxia 3 and machado-joseph disease: Clinical, molecular, and neuropathological features

1996 ◽  
Vol 39 (4) ◽  
pp. 490-499 ◽  
Author(s):  
Alexandra Durr ◽  
Giovanni Stevanin ◽  
Geraldine Cancel ◽  
Charles Duyckaerts ◽  
Nacer Abbas ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Machado Joseph Disease ◽  
Spinocerebellar Ataxia 3

scholarly journals Automated leg tracking reveals distinct conserved gait and tremor signatures in Drosophila models of Parkinson’s Disease and Spinocerebellar ataxia 3

2018 ◽  
Author(s):  
Shuang Wu ◽  
Kah Junn Tan ◽  
Lakshmi Narasimhan Govindarajan ◽  
James Charles Stewart ◽  
Lin Gu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Spinocerebellar Ataxia ◽  
Movement Disorders ◽  
High Speed ◽  
Molecular Mechanisms ◽  
Feature Learning ◽  
High Throughput Analysis ◽  
Abnormal Gait ◽  
Spinocerebellar Ataxia 3

SummaryGenetic models in Drosophila have made invaluable contributions to our understanding of the molecular mechanisms underlying neurodegeneration. In human patients, some neurodegenerative diseases lead to characteristic movement dysfunctions, such as abnormal gait and tremors. However, it is currently unknown whether similar movement defects occur in the respective fly models, which could be used to model and better understand the pathophysiology of movement disorders. To address this question, we developed a machine-learning image-analysis programme — Feature Learning-based LImb segmentation and Tracking (FLLIT) — that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, generating a series of body and leg movement parameters. Of note, FLLIT requires no user input for learning. We used FLLIT to characterise fly models of Parkinson’s Disease (PD) and Spinocerebellar ataxia 3 (SCA3). Between these models, walking gait and tremor characteristics differed markedly, and recapitulated signatures of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to phenotypes resembling that of PD flies, suggesting that the behavioural phenotype may depend on the circuits affected, rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits are affected. Almost 190,000 video frames were tracked in this study, allowing, for the first time, high-throughput analysis of gait and tremor features in Drosophila mutants. As an efficient assay of mutant gait and tremor features in an important model system, FLLIT will enable the analysis of the neurogenetic mechanisms that underlie movement disorders.

scholarly journals Flow cytometry allows rapid detection of protein aggregates in cellular and zebrafish models of spinocerebellar ataxia 3

2021 ◽  
Vol 14 (10) ◽  
Author(s):  
Katherine J. Robinson ◽  
Madelaine C. Tym ◽  
Alison Hogan ◽  
Maxinne Watchon ◽  
Kristy C. Yuan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Spinocerebellar Ataxia ◽  
Flow Cytometric Analysis ◽  
Protein Aggregates ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Transgenic Zebrafish ◽  
Flow Cytometric ◽  
Spinocerebellar Ataxia 3 ◽  
In Cells

ABSTRACT Spinocerebellar ataxia 3 (SCA3, also known as Machado–Joseph disease) is a neurodegenerative disease caused by inheritance of a CAG repeat expansion within the ATXN3 gene, resulting in polyglutamine (polyQ) repeat expansion within the ataxin-3 protein. In this study, we have identified protein aggregates in both neuronal-like (SHSY5Y) cells and transgenic zebrafish expressing human ataxin-3 with expanded polyQ. We have adapted a previously reported flow cytometry methodology named flow cytometric analysis of inclusions and trafficking, allowing rapid quantification of detergent insoluble forms of ataxin-3 fused to a GFP in SHSY5Y cells and cells dissociated from the zebrafish larvae. Flow cytometric analysis revealed an increased number of detergent-insoluble ataxin-3 particles per nuclei in cells and in zebrafish expressing polyQ-expanded ataxin-3 compared to those expressing wild-type human ataxin-3. Treatment with compounds known to modulate autophagic activity altered the number of detergent-insoluble ataxin-3 particles in cells and zebrafish expressing mutant human ataxin-3. We conclude that flow cytometry can be harnessed to rapidly count ataxin-3 aggregates, both in vitro and in vivo, and can be used to compare potential therapies targeting protein aggregates. This article has an associated First Person interview with the first author of the paper.

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