Loss of HRD1-Mediated Protein Degradation Causes Amyloid Precursor Protein Accumulation and Amyloid-β Generation

@article{Kaneko2010LossOH,
  title={Loss of HRD1-Mediated Protein Degradation Causes Amyloid Precursor Protein Accumulation and Amyloid-$\beta$ Generation},
  author={Masayuki Kaneko and Hiroshi Koike and Ryo Saito and Yoshihisa Kitamura and Yasunobu Okuma and Yasuyuki Nomura},
  journal={The Journal of Neuroscience},
  year={2010},
  volume={30},
  pages={3924 - 3932}
}
Endoplasmic reticulum-associated degradation (ERAD) is a system by which proteins accumulated in the endoplasmic reticulum (ER) are retrotranslocated to the cytosol and degraded by the ubiquitin–proteasome pathway. HRD1 is expressed in brain neurons and acts as an ERAD ubiquitin ligase. Amyloid precursor protein (APP) is processed into amyloid-β peptides (Aβs) that form plaque deposits in the brains of Alzheimer's disease (AD) patients. We found significantly decreased HRD1 protein levels in… 

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Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease: possible involvement of HRD1, a novel molecule related to endoplasmic reticulum stress, in Alzheimer's disease.
TLDR
The novel ubiquitin ligase HRD1, which is involved in ERAD, was cloned and it was shown thatHRD1 promoted amyloid precursor protein (APP) ubiquitination and degradation, resulting in decreased generation ofAmyloid β (Aβ) and suppression of HRD 1 expression caused APP accumulation and promoted Aβ generation associated with ER stress and apoptosis.
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