Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases
AbstractThe polyglutamine (polyQ) diseases, such as Huntington’s disease and several types of spinocerebellar ataxias, are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ tract in disease-causative proteins. Proteins with an abnormally expanded polyQ stretch undergo a conformational transition to β-sheet rich structure, which assemble into insoluble aggregates with β-sheet rich amyloid fibrillar structures and accumulate as inclusion bodies in neurons, eventually leading to neurodegeneration. Since misfolding and aggregation of the expanded polyQ proteins are the most upstream event in the most common pathogenic cascade of the polyQ diseases, they are proposed to be one of the most ideal targets for development of disease-modifying therapies for polyQ diseases. In this review, we summarize the current understanding of the molecular pathogenic mechanisms of the polyQ diseases, and introduce therapeutic approaches targeting misfolding and aggregation of the expanded polyQ proteins, which are not only effective on a wide spectrum of polyQ diseases, but also broadly correct the functional abnormalities of multiple downstream cellular processes affected in the aggregation process of polyQ proteins. We hope that in the near future, effective therapies are developed, to bring hope to many patients suffering from currently intractable polyQ diseases. View Full-Text
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Takeuchi, T.; Nagai, Y. Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases. Brain Sci. 2017, 7, 128.
Takeuchi T, Nagai Y. Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases. Brain Sciences. 2017; 7(10):128.Chicago/Turabian Style
Takeuchi, Toshihide; Nagai, Yoshitaka. 2017. "Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases." Brain Sci. 7, no. 10: 128.
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