Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.

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Version: Final published version
Serval ID
serval:BIB_9D3AFCAEBB95
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.
Journal
Human Molecular Genetics
Author(s)
Francelle L., Galvan L., Gaillard M.C., Guillermier M., Houitte D., Bonvento G., Petit F., Jan C., Dufour N., Hantraye P., Elalouf J.M., De Chaldée M., Déglon N., Brouillet E.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
02/2015
Peer-reviewed
Oui
Volume
24
Number
6
Pages
1563-1573
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patients.
Pubmed
Web of science
Open Access
Yes
Create date
15/12/2014 14:22
Last modification date
20/08/2019 15:03
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