Carnemolla, A;
Michelazzi, S;
Agostoni, E;
(2017)
PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An In vitro Model.
Frontiers in Cellular Neuroscience
, 11
, Article 121. 10.3389/fncel.2017.00121.
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Abstract
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a polyglutamine expansion within the N-terminal region of huntingtin protein (HTT). Cellular mechanisms promoting mutant huntingtin (mHTT) clearance are of great interest in HD pathology as they can lower the level of the mutant protein and its toxic aggregated species, thus affecting disease onset and progression. We have previously shown that the prolyl-isomerase PIN1 represents a promising negative regulator of mHTT aggregate accumulation using a genetically precise HD mouse model, namely HdhQ111 mice. Therefore, the current study aims at underpinning the mechanism by which PIN1 affects huntingtin’s aggregates. We found that PIN1 overexpression led to a reduction of mHTT aggregates in HEK293 cells, and that this could be linked to a negative regulation of mHTT half-life by PIN1. Furthermore, we show that PIN1 has the ability to stimulate the proteasome presenting evidence of a mechanism regulating this phenomenon. Our findings provide a rationale for future investigation into PIN1 with the potential for the development of novel therapeutic strategies.
| Type: | Article |
|---|---|
| Title: | PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An In vitro Model |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fncel.2017.00121 |
| Publisher version: | http://dx.doi.org/10.3389/fncel.2017.00121 |
| Language: | English |
| Additional information: | © 2017 Carnemolla, Michelazzi and Agostoni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Huntingtin, aggregates, PIN1, Huntington’s disease, proteasome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10043442 |
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