BRIEF RESEARCH REPORT article
Front. Genet.
Sec. RNA
This article is part of the Research TopicInsights in RNA: 2025View all 4 articles
Aberrant expression of the MID1 protein in neurons of Huntington's disease brain
Provisionally accepted
- University of Siegen, Siegen, Germany
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Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the Huntingtin (HTT) gene that transcribes into mRNA and translates into a polyglutamine tract. The mutant HTT gene products drive pathological changes that result in neurodegeneration. The mutant CAG repeat RNA contributes to cellular dysfunction by aberrantly recruiting RNA-binding proteins. For example, the mutant HTT transcript associates with a protein complex containing the MID1 protein. This aberrant recruitment of the MID1 protein complex results in an increased translation of mutant HTT. MID1 expression is abnormally high in both the brains of HD mouse models and HD patients. However, the cell type in which MID1 is overexpressed in HD brains remains obscure. Here, we investigated the MID1 expression in different brain cell types of an HD mouse model. Therefore, we separated neurons, astrocytes and microglia via magnetic sorting and show that MID1 is overexpressed in neurons of an HD mouse model. Moreover, we stained MID1 in brain sections of HD mice via immunohistochemistry and observed MID1 overexpressing cells in cortex. This finding shows that MID1 is highly expressed in neurons – the most vulnerable cell type in HD – underlining its important role in the neurodegenerative process. This supports the concept of blocking the interaction between MID1 and mutant HTT mRNA to counteract mutant HTT translation as a promising therapeutic approach.
Keywords: Huntington's disease, MID1, RNA-Binding Protein, translation regulation, Ubiquitinligase
Received: 24 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Reisbitzer, Geraci and Krauß. 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.
* Correspondence: Sybille Krauß
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