Correlation between decrease in protein levels of ubiquitin ligase HRD1 and amyloid-beta production.

Endoplasmic reticulum-associated degradation (ERAD) is a quality control mechanism in which unfolded proteins are retro-translocated to the cytosol for degradation. Our recent study showed that suppression of expression of ubiquitin ligase HRD1, which is involved in ERAD, caused amyloid precursor protein (APP) accumulation and amyloid-beta (Abeta) production. Furthermore, HRD1 protein levels were significantly lower in the cerebral cortex of Alzheimer's disease (AD) patients. To assess whether HRD1 is involved in AD pathology, we analyzed the relationship between HRD1 protein levels and Abeta production. We found that the HRD1 level was negatively correlated with the Abeta level, suggesting the possible involvement of HRD1 in Abeta generation.