例如:"lncRNA", "apoptosis", "WRKY"

CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration.

J. Neurochem.2014 Jun;129(6):1013-23. doi:10.1111/jnc.12684. Epub 2014 Mar 24
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
+ et al

[No authors listed]

Author information
  • {{index+1}} {{ organisation }}

摘要


Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytosolic inclusion bodies and cell death in distinct neuronal populations. Since cyclin-dependent kinase-5 (CDK5) has been shown to exert beneficial effects on aggregate formation and cell death in various polyglutamine diseases, we tested its therapeutic potential for SCA3. Our data show increased caspase-dependent Ataxin-3 cleavage, aggregation, and neurodegeneration in the absence of sufficient CDK5 activity. This disease-propagating effect could be reversed by mutation of the caspase cleavage site in Ataxin-3. Moreover, reduction of CDK5 expression levels by in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. In summary, we present CDK5 as a potent neuroprotectant, regulating cleavage and thereby toxicity of Ataxin-3 and other polyglutamine proteins. We propose that increased caspase-dependent cleavage of mutated Ataxin-3, because of missing CDK5 shielding, leads to aggregation and cell death. Moreover, reduction of CDK5 expression levels by duanyu1615 in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. We think that CDK5 functions as a shield against cleavage-induced toxification and thereby is an interesting target for therapeutic intervention in polyQ disease in general.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}

基因功能


  • {{$index+1}}.{{ gene }}

图表


原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
{{attr}}
{{ dataList.sampleTitle }}
{{ dataList.organism }} {{ dataList.expermentTitle }} {{ dataList.sampleType }} {{ dataList.libraryInstrument }} {{ showAttributeName(index,attr,dataList.attributes) }}

文献解读