Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions
Abstract
:1. Introduction
2. SCA10
2.1. Patient Demographics, Clinical Presentation, and Neuropathology
2.2. SCA10 Repeat Origin and Structures
2.3. RNA Gain-of-Function in SCA10 Cells and Animal Models
2.4. Proposed Models of SCA10 Repeat Expansion
2.5. Theranostic Development for SCA10
3. SCA31
3.1. Patient Demographics and Neuropathological Features
3.2. RNA Gain-of-Function and Pentapeptide Repeat Protein in SCA31
3.3. Interplay between SCA31 RNA Expansion and RNA Binding Proteins
3.4. Small Molecule Targeting UGGAA in SCA31
4. SCA37
4.1. Clinical Presentation and Neuropathology
4.2. RNA Toxicity and Dysregulation of DAB1 Expression in SCA37
5. CANVAS
5.1. Clinical Presentation and Neuropathology
5.2. Repeat Polymorphism and Intron Retention for CANVAS
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | Gene (Locus) | Pathogenic Repeat Range |
---|---|---|
SCA10 | Intron 9 of ATXN10 (22q13.31) | ATTCT800–4500 |
SCA31 | ntron shared by BEAN & TK2 (16q22.1) | TGGAAn |
SCA37 | 5′-UTR intron 1 or 3 of DAB1 (1p32.2) | ATTTC31–75 |
CANVAS | Intron 2 of RFC1 (4p14) | AAGGG400–2000 |
ACAGG~1000 | ||
AAAGG10–25AAGGGnAAAGGn |
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Zhang, N.; Ashizawa, T. Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions. Cells 2022, 11, 1567. https://doi.org/10.3390/cells11091567
Zhang N, Ashizawa T. Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions. Cells. 2022; 11(9):1567. https://doi.org/10.3390/cells11091567
Chicago/Turabian StyleZhang, Nan, and Tetsuo Ashizawa. 2022. "Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions" Cells 11, no. 9: 1567. https://doi.org/10.3390/cells11091567
APA StyleZhang, N., & Ashizawa, T. (2022). Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions. Cells, 11(9), 1567. https://doi.org/10.3390/cells11091567