Dementia Research Today is a free monthly online journal that collates and summarizes the latest research about Dementia, including details on symptoms, alzheimers, senile dementia, causes.

Testing the possible inhibition of proteasome by direct interaction with ubiquitylated and aggregated huntingtin.

Valera AG, Díaz-Hernández M, Hernández F, Lucas JJ

Centro de Biologia Molecular Severo Ochoa, CSIC/UAM, Campus UAM de Cantoblanco, Madrid, Spain.

An impairment of the ubiquitin-proteasome system (UPS) has been postulated in Huntington's disease (HD) and in other CAG-triplet repeat disorders. This hypothesis arises from the observation that polyglutamine (polyQ)-containing inclusion bodies that are characteristic of these diseases also contain components of the UPS. However, since that initial discovery, the UPS impairment hypothesis has remained controversial. Recent in vitro enzymatic studies revealed the inability of eukaryotic proteasomes to digest expanded polyQ, thus suggesting that occasional failure of polyQ to exit the proteasome may interfere with its proteolytic function. However, it has also recently been found that in vitro assembled aggregates made of synthetic polyQ fail to inhibit proteasome activity. Here we propose future experiments that may help to ellucidate whether a direct interaction between proteasomes and polyQ stretches or aggregates can result in inhibition of proteasome activity.

Published 13 March 2007 in Brain Res Bull, 72(2): 121-3.
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