Journal article

Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation

Mona Radwan, Jordan D Lilley, Ching-Seng Ang, Gavin E Reid, Danny M Hatters



Poly(glycine-alanine) (polyGA) is one of the polydipeptides expressed in Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 1 caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ)-expanded Huntingtin exon 1 (Httex1) in Huntington's disease. Both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms and therefore recruit the same repertoire of endogenous proteins. When co-expressed in the same cell, polyGA101 and Httex1(Q97) inclusions adopted immiscible phases suggesting different endogenous proteins would be e..

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Awarded by National Health and Medical Research Council

Awarded by Australian Research Council

Funding Acknowledgements

This work was funded by grants to DMH (National Health and Medical Research Council APP1161803 ( and Motor Neuron Disease Research Institute, Australia small grant ( and to DMH and GER (Australian Research Council DP170103093) ( MR acknowledges support from an Australian Government Research Training Program (RTP) Scholarship via the University of Melbourne ( and an Egyptian Ministry of Higher Education and Scientific Research PhD scholarship ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.