著作: Namekata Kazuhiko/[西村 範行]/Kimura Hideo/Presenilin-binding protein forms aggresomes in monkey kidney COS-7 cells/[Journal of Neurochemistry]
(英) Presenilin-binding protein forms aggresomes in monkey kidney COS-7 cells
(英) A novel presenilin-binding protein (PBP) is specifically expressed in the brain, and its level in the soluble fraction of Alzheimer's disease (AD) brains is much less than that in the age-matched controls. Recently, several proteins, including presenilin (PS), have been found to form structures of aggregated proteins, called aggresomes, when the production of the proteins exceeds their rate of degradation by proteasomes. Based on these observations it has been proposed that the aggresome may represent one of the mechanisms forthe formation of cytoplasmic deposits which are linked to the pathogenesis of neurodegenerative disorders including AD. It is shown here that the overexpression of PBP or the suppression of proteasome activity in monkey kidney COS-7 cells leads to the accumulation of detergent-insoluble and multiubiquitinated PBP aggregates. PBP also forms aggregates in primary cultures of neurons in the presence of a proteasome inhibitors. PBP aggregates have the characteristics of aggresomes, including the localization to microtubule organization centers and the disruption of intermediate filaments. These observations suggest that the malfunctioning of the proteasome can cause the formation of PBP aggresomes, which may lead to AD.
|発行所||推奨||The International Society for Neurochemistry|
Journal of Neurochemistry([The International Society for Neurochemistry])
|年月日||必須||2002年 8月 初日|