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Updated: Jun 20, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Turning REST/NRSF dysfunction in Huntington's disease into a pharmaceutical target
Dorotea Rigamonti1, Cesare Mutti, Chiara Zuccato
1Università degli Studi di Milano, Dipartimento di Scienze Farmacologiche e Centro di Ricerca sulle Cellule Staminali, via Balzaretti 9, 20133 Milano.
Current Pharmaceutical Design
|September 16, 2009
Summary
Huntington's Disease involves REST/NRSF silencing neuronal genes. Researchers are developing drugs targeting this transcription factor to restore gene expression and treat brain degeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- REST/NRSF is a transcription factor that silences neuronal genes by binding to RE1/NRSE DNA elements.
- In Huntington's Disease, aberrant REST/NRSF nuclear entry silences crucial neuronal genes, contributing to neurodegeneration.
Purpose of the Study:
- To review the rationale for targeting the REST/NRSF-RE1/NRSE system in Huntington's Disease.
- To explore rational drug design strategies for developing therapeutics against REST/NRSF-mediated gene silencing.
Main Methods:
- Review of existing literature on REST/NRSF function and its role in Huntington's Disease.
- Discussion of potential therapeutic strategies targeting REST/NRSF activity.
Main Results:
- The REST/NRSF-RE1/NRSE pathway is a validated target for Huntington's Disease intervention.
- Multiple drug design strategies are being pursued, focusing on REST/NRSF nuclear translocation, DNA binding, or complex formation.
Conclusions:
- Developing small molecules to modulate REST/NRSF activity holds promise for restoring neuronal gene transcription.
- Targeting the REST/NRSF pathway offers a potential therapeutic avenue for neurodegenerative conditions like Huntington's Disease.
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