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Updated: Jun 28, 2026

Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity
Published on: September 21, 2021
Human receptor for activated protein kinase C1 associates with polyglutamine aggregates and modulates polyglutamine
Wun Lam1, Wing Man Chan1, Tsz Wai Lo1
1Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Abstract:
Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer's and Parkinson's diseases.
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