Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies
Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/9/3063 |
| _version_ | 1797569601760919552 |
|---|---|
| author | Yu-Shuan Chen Zhen-Xiang Hong Shinn-Zong Lin Horng-Jyh Harn |
| author_facet | Yu-Shuan Chen Zhen-Xiang Hong Shinn-Zong Lin Horng-Jyh Harn |
| author_sort | Yu-Shuan Chen |
| collection | DOAJ |
| description | Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes. The three major conclusions from the current studies are summarized as follows: (i) for the drugs currently being tested in clinical trials; a weak connection was observed between drugs and SCA3/MJD biomarkers. The only two exceptions are the drugs suppressing glutamate-induced calcium influx and chemical chaperon. (ii) For most of the drugs that have been tested in animal studies, there is a direct association with pathological biomarkers. We further found that many drugs are associated with inducing autophagy, which is supported by the evidence of deficient autophagy biomarkers in SCA3/MJD, and that there may be more promising therapeutics. (iii) Some reported biomarkers lack relatively targeted drugs. Low glucose utilization, altered amino acid metabolism, and deficient insulin signaling are all implicated in SCA3/MJD, but there have been few studies on treatment strategies targeting these abnormalities. Therapeutic strategies targeting multiple pathological SCA3/MJD biomarkers may effectively block disease progression and preserve neurological function. |
| first_indexed | 2024-03-10T20:12:54Z |
| format | Article |
| id | doaj.art-e0c0934fcd3d45969581ccee4dcd8aa0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:12:54Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e0c0934fcd3d45969581ccee4dcd8aa02023-11-19T22:47:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219306310.3390/ijms21093063Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic StrategiesYu-Shuan Chen0Zhen-Xiang Hong1Shinn-Zong Lin2Horng-Jyh Harn3Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 97002, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 97002, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 97002, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 97002, TaiwanSpinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes. The three major conclusions from the current studies are summarized as follows: (i) for the drugs currently being tested in clinical trials; a weak connection was observed between drugs and SCA3/MJD biomarkers. The only two exceptions are the drugs suppressing glutamate-induced calcium influx and chemical chaperon. (ii) For most of the drugs that have been tested in animal studies, there is a direct association with pathological biomarkers. We further found that many drugs are associated with inducing autophagy, which is supported by the evidence of deficient autophagy biomarkers in SCA3/MJD, and that there may be more promising therapeutics. (iii) Some reported biomarkers lack relatively targeted drugs. Low glucose utilization, altered amino acid metabolism, and deficient insulin signaling are all implicated in SCA3/MJD, but there have been few studies on treatment strategies targeting these abnormalities. Therapeutic strategies targeting multiple pathological SCA3/MJD biomarkers may effectively block disease progression and preserve neurological function.https://www.mdpi.com/1422-0067/21/9/3063spinocerebellar ataxia type 3/Machado–Joseph diseasetherapeutic strategiespathological biomarkers |
| spellingShingle | Yu-Shuan Chen Zhen-Xiang Hong Shinn-Zong Lin Horng-Jyh Harn Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies International Journal of Molecular Sciences spinocerebellar ataxia type 3/Machado–Joseph disease therapeutic strategies pathological biomarkers |
| title | Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies |
| title_full | Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies |
| title_fullStr | Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies |
| title_full_unstemmed | Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies |
| title_short | Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies |
| title_sort | identifying therapeutic targets for spinocerebellar ataxia type 3 machado joseph disease through integration of pathological biomarkers and therapeutic strategies |
| topic | spinocerebellar ataxia type 3/Machado–Joseph disease therapeutic strategies pathological biomarkers |
| url | https://www.mdpi.com/1422-0067/21/9/3063 |
| work_keys_str_mv | AT yushuanchen identifyingtherapeutictargetsforspinocerebellarataxiatype3machadojosephdiseasethroughintegrationofpathologicalbiomarkersandtherapeuticstrategies AT zhenxianghong identifyingtherapeutictargetsforspinocerebellarataxiatype3machadojosephdiseasethroughintegrationofpathologicalbiomarkersandtherapeuticstrategies AT shinnzonglin identifyingtherapeutictargetsforspinocerebellarataxiatype3machadojosephdiseasethroughintegrationofpathologicalbiomarkersandtherapeuticstrategies AT horngjyhharn identifyingtherapeutictargetsforspinocerebellarataxiatype3machadojosephdiseasethroughintegrationofpathologicalbiomarkersandtherapeuticstrategies |