Repressor element‐1 silencing transcription factor (REST) is present in human control and Huntington's disease neurones. Issue 7 (17th November 2014)

• Record Type: Journal Article
• Authors: Schiffer, Davide; Caldera, Valentina; Mellai, Marta; Conforti, Paola; Cattaneo, Elena; Zuccato, Chiara
• Is Part Of: Neuropathology & applied neurobiology. Volume 40:Issue 7(2014)
• Page Start: 899
• Page End: 910
• Publication Date: 2014-11-17
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12137
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="nan12137-sec-0001" sec-type="section"> <title>Aims</title> <p>The repressor element‐1 silencing transcription factor/neurone‐restrictive silencer factor (REST/NRSF) is a master regulator of neuronal gene expression. REST/NRSF functions by recruiting other cofactors to genomic loci that contain the repressor element 1/neurone restrictive silencer element (RE1/NRSE) binding motif. In brain, demonstration of REST protein presence in neurones has remained controversial. However, RE1/NRSE containing neuronal genes are actively modulated and REST dysregulation is implicated in Huntington's disease (HD). We aimed to investigate REST distribution in autopsy brain from control and HD patients.</p> </sec> <sec id="nan12137-sec-0002" sec-type="section"> <title>Methods</title> <p>Brain tissues from six controls and six HD cases (Vonsattel grade 3 and 4) were investigated using immunohistochemical analysis.</p> </sec> <sec id="nan12137-sec-0003" sec-type="section"> <title>Results</title> <p>REST was present in neurones and glial cells of the cortex, caudate nucleus, hippocampus and cerebellum. REST labelling was mainly cytoplasmic in neurones while preferential nuclear staining of REST was found in glial cells. We also found that REST and huntingtin (HTT) colocalize in human neurones. Low levels of cytoplasmic REST were detected in neurones of the HD cortex and caudate but no direct relationship between decreased neuronal REST expression and disease grade was observed.</p> </sec> <sec id="nan12137-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These data support the notion of REST presence in human brain neurones and glial cells and indicate the importance of developing compounds able to restore REST‐regulated transcription of neuronal genes in HD.</p> </sec> </abstract>