Viewing the Cellular Responses in Huntington's Disease Through an Aggreomics Framework

A biosensor-based framework to measure latent proteostasis capacity

RJ Wood, AR Ormsby, M Radwan, D Cox, A Sharma, T Vöpel, S Ebbinghaus, M Oliveberg, GE Reid, A Dickson, DM Hatters

2018-12-01

The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depl..

A thiol probe for measuring unfolded protein load and proteostasis in cells

MZ Chen, NS Moily, JL Bridgford, RJ Wood, M Radwan, TA Smith, Z Song, BZ Tang, L Tilley, X Xu, GE Reid, MA Pouladi, Y Hong, DM Hatters

2017-12-01

When proteostasis becomes unbalanced, unfolded proteins can accumulate and aggregate. Here we report that the dye, tetraphenylethe..

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

2017-09-01

Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The c..

Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis

YM Ramdzan, MM Trubetskov, AR Ormsby, EA Newcombe, X Sui, MJ Tobin, MN Bongiovanni, SL Gras, G Dewson, JML Miller, S Finkbeiner, NS Moily, J Niclis, CL Parish, AW Purcell, MJ Baker, JA Wilce, S Waris, D Stojanovski, T Böcking

2017-05-02

Competing models exist in the literature for the relationship between mutant Huntingtin exon 1 (Httex1) inclusion formation and to..

When proteostasis goes bad: Protein aggregation in the cell

M Radwan, RJ Wood, X Sui, DM Hatters

2017-02-01

Protein aggregation is a hallmark of the major neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and mot..

Conformational dynamics and self-association of intrinsically disordered Huntingtin exon 1 in cells

S Büning, A Sharma, S Vachharajani, E Newcombe, A Ormsby, M Gao, D Gnutt, T Vöpel, DM Hatters, S Ebbinghaus

2017-01-01

Huntington's disease is caused by a CAG trinucleotide expansion mutation in the Huntingtin gene that leads to an artificially long..

N-terminal fragments of huntingtin longer than residue 170 form visible aggregates independently to polyglutamine expansion

MZ Chen, SA Mok, AR Ormsby, PJ Muchowski, DM Hatters

2017-01-01

Background: A hallmark of Huntington's disease is the progressive aggregation of full length and N-terminal fragments of polygluta..

Walking the tightrope: Proteostasis and neurodegenerative disease

JJ Yerbury, L Ooi, A Dillin, DN Saunders, DM Hatters, PM Beart, NR Cashman, MR Wilson, H Ecroyd

2016-05-01

A characteristic of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's di..

Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation

S Polling, AR Ormsby, RJ Wood, K Lee, C Shoubridge, JN Hughes, PQ Thomas, MDW Griffin, AF Hill, Q Bowden, T Böcking, DM Hatters

2015-12-01

Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to for..

Misfolded polyglutamine, polyalanine, and superoxide dismutase 1 aggregate via distinct pathways in the cell

S Polling, YF Mok, YM Ramdzan, BJ Turner, JJ Yerbury, AF Hill, DM Hatters

2014-03-07

Background: Protein aggregation is associated with neurodegenerative diseases. Results:Wedefined how the oligomeric state of disea..

A platform to view huntingtin exon 1 aggregation flux in the cell reveals divergent influences from chaperones hsp40 and hsp70

AR Ormsby, YM Ramdzan, YF Mok, KD Jovanoski, DM Hatters

2013-12-27

Background: How misfolded proteins such as mutant huntingtin aggregate in the cell remains enigmatic. Results:Webuilt a platform t..

Tyrosine 416 Is Phosphorylated in the Closed, Repressed Conformation of c-Src

S Irtegun, RJ Wood, AR Ormsby, TD Mulhern, DM Hatters

2013-07-26

c-Src kinase activity is regulated by phosphorylation of Y527 and Y416. Y527 phosphorylation stabilizes a closed conformation, whi..

Putting huntingtin "aggregation" in view with windows into the cellular milieu

DM Hatters

2012-12-01

Huntington's disease arises from CAG codon-repeat expansions in the Htt gene, which leads to a Htt gene product with an expanded p..