Transcriptional profiles for distinct aggregation states of mutant Huntingtin exon 1 protein unmask new Huntington's disease pathways

NS Moily; AR Ormsby; A Stojilovic; YM Ramdzan; J Diesch; RD Hannan; MS Zajac; AJ Hannan; A Oshlack; DM Hatters

Journal article

Transcriptional profiles for distinct aggregation states of mutant Huntingtin exon 1 protein unmask new Huntington's disease pathways

NS Moily, AR Ormsby, A Stojilovic, YM Ramdzan, J Diesch, RD Hannan, MS Zajac, AJ Hannan, A Oshlack, DM Hatters

Molecular and Cellular Neuroscience | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2017

DOI: 10.1016/j.mcn.2017.07.004

Abstract

Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The central feature of Huntington's disease pathology is the aggregation of mutant Huntingtin (Htt) protein into micrometer-sized inclusion bodies. Soluble mutant Htt states are most proteotoxic and trigger an enhanced risk of death whereas inclusions confer different changes to cellular health, and may even provide adaptive responses to stress. Yet the molecular mechanisms underpinning these changes remain unclear. Using the flow cytometry method of pulse-shape analysis (PulSA) to sort neuroblastoma (Neuro2a) cells enriched with mutant or wild-type Htt into different ..

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University of Melbourne Researchers

Anthony Hannan Author

Alicia Oshlack Author

Danny M Hatters Author

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Grants

Awarded by Hereditary Disease Foundation

Funding Acknowledgements

This work was supported by grants to DMH from the Australian Research Council (grant number FT120100039); grants/fellowships from the National Health and Medical Research Council Project to DMH (grant numbers APP1049458, APP1049459 and APP1102059), and a grant from the Hereditary Disease Foundation (USA). AJH is an NHMRC Principal Research Fellow.