OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Reducing mutant huntingtin protein expression in living cells by a newly identified RNA CAG binder.

PuSH - Publication Server of Helmholtz Zentrum München

Matthes, F.* ; Massari, S.* ; Bochicchio, A.* ; Schorpp, K.K. ; Schilling, J.* ; Weber, S.* ; Offermann, N.* ; Desantis, J.* ; Wanker, E.* ; Carloni, P.* ; Hadian, K. ; Tabarrini, O.* ; Rossetti, G.* ; Krauss, S.*

Reducing mutant huntingtin protein expression in living cells by a newly identified RNA CAG binder.

ACS Chem. Neurosci. 9, 1399-1408 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Expanded CAG trinucleotide repeats in Huntington's disease (HD) are causative for neurotoxicity. The mutant CAG repeat RNA encodes neurotoxic polyglutamine proteins and can lead to a toxic gain of function by aberrantly recruiting RNA-binding proteins. One of these is the MID1 protein, which induces aberrant Huntingtin (HTT) protein translation upon binding. Here we have identified a set of CAG repeat binder candidates by in silico methods. One of those, furamidine, reduces the level of binding of HTT mRNA to MID1 and other target proteins in vitro. Metadynamics calculations, fairly consistent with experimental data measured here, provide hints about the binding mode of the ligand. Importantly, furamidine also decreases the protein level of HTT in a HD cell line model. This shows that small molecules masking RNA-MID1 interactions may be active against mutant HTT protein in living cells.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Furamidine ; Huntingtin Protein ; Huntington's Disease ; Living Cell Experiments ; Metadynamics-based Free Energy Calculations ; Rna-mid1 Interactions
e-ISSN 1948-7193
Journal ACS Chemical Neuroscience
Quellenangaben Volume: 9, Issue: 6, Pages: 1399-1408 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)