Journal article

N-Terminal Fragments of Huntingtin Longer than Residue 170 form Visible Aggregates Independently to Polyglutamine Expansion

Moore Z Chen, Sue-Ann Mok, Angelique R Ormsby, Paul J Muchowski, Danny M Hatters

JOURNAL OF HUNTINGTONS DISEASE | IOS PRESS | Published : 2017

Abstract

BACKGROUND: A hallmark of Huntington's disease is the progressive aggregation of full length and N-terminal fragments of polyglutamine (polyQ)-expanded Huntingtin (Htt) into intracellular inclusions. The production of N-terminal fragments appears important for enabling pathology and aggregation; and hence the direct expression of a variety of N-terminal fragments are commonly used to model HD in animal and cellular models. OBJECTIVE: It remains unclear how the length of the N-terminal fragments relates to polyQ - mediated aggregation. We investigated the fundamental intracellular aggregation process of eight different-length N-terminal fragments of Htt in both short (25Q) and long polyQ (97Q..

View full abstract

Grants

Awarded by Australian Research Council Discovery: Future Fellowships


Awarded by National Health and Medical Research Council


Funding Acknowledgements

We would like to thank Steven Finkbeiner from the Gladstone Institute of Neurological Disease for provision of the pGW1-based N90 vectors fused to mCherry. This work was funded by grants to DMH from the Australian Research Council Discovery: Future Fellowships FT120100039, National Health and Medical Research Council Project grants APP1049458, APP1049459 and APP1102059 and the Hereditary Disease Foundation. These funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.