Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy.

Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy. Int J Mol Med. 2019 Oct 15;: Authors: Carbo M, Brandi V, Pascarella G, Staid DS, Colotti G, Polticelli F, Ilari A, Morea V Abstract Huntington's disease (HD) is a lethal neurodegenerative disorder for which no cure is available yet. It is caused by abnormal expansion of a CAG triplet in the gene encoding the huntingtin protein (Htt), with consequent expansion of a polyglutamine repeat in mutated Htt (mHtt). This makes mHtt highly unstable and aggregation prone. Soluble mHtt is linked to cytotoxicity and neurotoxicity, whereas mHtt aggregates are thought to be neuroprotective. While Htt and mHtt are ubiquitously expressed throughout the brain and peripheral tissues, HD is characterized by selective degradation of the corpus striatum, without notable alterations in peripheral tissues. Screening for mRNAs preferentially expressed in rodent striatum led to the discovery of a GTP binding protein homologous to Ras family members. Due to these features, the newly discovered protein was termed Ras Homolog Enriched in Striatum (RHES). The aetiological role of RHES in HD has been ascribed to its small ubiquitin‑like modifier (SUMO)‑E3 ligase function. RHES sumoylates mHtt with higher efficiency than wild‑type Htt, thereby protecting mHtt from degradation and increasing the amounts of the soluble form. Although RHES is a...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research