Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions
Pentanucleotide expansion diseases constitute a special class of neurodegeneration. The repeat expansions occur in non-coding regions, have likely arisen from <i>Alu</i> elements, and often result in autosomal dominant or recessive phenotypes with underlying cerebellar neuropathology. Wh...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1567 |
| _version_ | 1827672854525640704 |
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| author | Nan Zhang Tetsuo Ashizawa |
| author_facet | Nan Zhang Tetsuo Ashizawa |
| author_sort | Nan Zhang |
| collection | DOAJ |
| description | Pentanucleotide expansion diseases constitute a special class of neurodegeneration. The repeat expansions occur in non-coding regions, have likely arisen from <i>Alu</i> elements, and often result in autosomal dominant or recessive phenotypes with underlying cerebellar neuropathology. When transcribed (potentially bidirectionally), the expanded RNA forms complex secondary and tertiary structures that can give rise to RNA-mediated toxicity, including protein sequestration, pentapeptide synthesis, and mRNA dysregulation. Since several of these diseases have recently been discovered, our understanding of their pathological mechanisms is limited, and their therapeutic interventions underexplored. This review aims to highlight new in vitro and in vivo insights into these incurable diseases. |
| first_indexed | 2024-03-10T04:16:07Z |
| format | Article |
| id | doaj.art-83c096b44afd4c679ace22cf396ec8f9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:16:07Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-83c096b44afd4c679ace22cf396ec8f92023-11-23T08:01:07ZengMDPI AGCells2073-44092022-05-01119156710.3390/cells11091567Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide ExpansionsNan Zhang0Tetsuo Ashizawa1Neuroscience Research Program, Department of Neurology, Houston Methodist Research Institute, Weil Cornell Medical College, Houston, TX 77030, USANeuroscience Research Program, Department of Neurology, Houston Methodist Research Institute, Weil Cornell Medical College, Houston, TX 77030, USAPentanucleotide expansion diseases constitute a special class of neurodegeneration. The repeat expansions occur in non-coding regions, have likely arisen from <i>Alu</i> elements, and often result in autosomal dominant or recessive phenotypes with underlying cerebellar neuropathology. When transcribed (potentially bidirectionally), the expanded RNA forms complex secondary and tertiary structures that can give rise to RNA-mediated toxicity, including protein sequestration, pentapeptide synthesis, and mRNA dysregulation. Since several of these diseases have recently been discovered, our understanding of their pathological mechanisms is limited, and their therapeutic interventions underexplored. This review aims to highlight new in vitro and in vivo insights into these incurable diseases.https://www.mdpi.com/2073-4409/11/9/1567neurodegenerationmicrosatellite expansion diseasespentanucleotide repeatsspinocerebellar ataxiaSCA10SCA31 |
| spellingShingle | Nan Zhang Tetsuo Ashizawa Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions Cells neurodegeneration microsatellite expansion diseases pentanucleotide repeats spinocerebellar ataxia SCA10 SCA31 |
| title | Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions |
| title_full | Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions |
| title_fullStr | Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions |
| title_full_unstemmed | Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions |
| title_short | Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions |
| title_sort | mechanistic and therapeutic insights into ataxic disorders with pentanucleotide expansions |
| topic | neurodegeneration microsatellite expansion diseases pentanucleotide repeats spinocerebellar ataxia SCA10 SCA31 |
| url | https://www.mdpi.com/2073-4409/11/9/1567 |
| work_keys_str_mv | AT nanzhang mechanisticandtherapeuticinsightsintoataxicdisorderswithpentanucleotideexpansions AT tetsuoashizawa mechanisticandtherapeuticinsightsintoataxicdisorderswithpentanucleotideexpansions |