Yu Li

Publications (3)10.72 Total impact

• Article: BACE1 Gene Promoter Single-Nucleotide Polymorphisms in Alzheimer’s Disease

  Weihui Zhou, Fang Cai, Yu Li, George S. Yang, Kathleen D. O’Connor, Robert A. Holt, Weihong Song
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  ABSTRACT: Alzheimer’s disease (AD) is the most neurodegenerative disorder leading to dementia. Neuritic plaque formation in brains is a hallmark of AD pathogenesis. Amyloid β protein (Aβ) is the central component of neuritic plaques. Processing β-amyloid precursor protein (APP) at the β-secretase site by the beta-site APP cleaving enzyme 1 (BACE1) is essential for generation of Aβ. Elevation of BACE1 activity and expression has been reported in AD brains. However, no mutation in the BACE1 coding sequence has been identified in AD cases. Human BACE1 expression is tightly regulated at the transcription and translation level. To determine whether there is any single-nucleotide polymorphisms in the BACE1 gene promoter region affecting BACE1 expression in AD pathogenesis, in this study, we screened 2.6kb of the human BACE1 gene promoter region from late-onset AD patients and found that there was no significant association between single-nucleotide polymorphisms and AD cases. KeywordsBACE1-Promoter-Single-nucleotide polymorphisms-Alzheimer’s disease
  Journal of Molecular Neuroscience 04/2012; 42(1):127-133. · 2.50 Impact Factor
• Article: BACE1 gene promoter single-nucleotide polymorphisms in Alzheimer's disease.

  Weihui Zhou, Fang Cai, Yu Li, George S Yang, Kathleen D O'Connor, Robert A Holt, Weihong Song
  [show abstract] [hide abstract]
  ABSTRACT: Alzheimer's disease (AD) is the most neurodegenerative disorder leading to dementia. Neuritic plaque formation in brains is a hallmark of AD pathogenesis. Amyloid beta protein (Abeta) is the central component of neuritic plaques. Processing beta-amyloid precursor protein (APP) at the beta-secretase site by the beta-site APP cleaving enzyme 1 (BACE1) is essential for generation of Abeta. Elevation of BACE1 activity and expression has been reported in AD brains. However, no mutation in the BACE1 coding sequence has been identified in AD cases. Human BACE1 expression is tightly regulated at the transcription and translation level. To determine whether there is any single-nucleotide polymorphisms in the BACE1 gene promoter region affecting BACE1 expression in AD pathogenesis, in this study, we screened 2.6 kb of the human BACE1 gene promoter region from late-onset AD patients and found that there was no significant association between single-nucleotide polymorphisms and AD cases.
  Journal of Molecular Neuroscience 05/2010; 42(1):127-33. · 2.50 Impact Factor
• Article: Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription.

  Yu Li, Weihui Zhou, Yigang Tong, Guiqiong He, Weihong Song
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  ABSTRACT: Deposition of amyloid beta protein (Abeta) is one of the characteristic features of Alzheimer's disease (AD) neuropathology. Beta-secretase, a beta-site APP cleaving enzyme 1 (BACE1), is essential for Abeta biosynthesis. Although inhibition of BACE1 is considered a valid therapeutic target for AD, the enzymatic dynamics of BACE1 in regulating APP processing and Abeta generation has not yet been fully defined. To examine this issue, tightly controlled inducible BACE1 gene expression was established in the neuronal cell line N2ABP1 and the non-neuronal cell line E2BP1 using an ecdysone-inducible system. The BACE1 protein level was increased in a time- and dosage-dependent manner in the inducible BACE1 stable cells by treatment with inducer ponasterone A. The generation of APP CTFbeta, the beta-secretase product, increased proportionally with the level of BACE1 protein expression. However, Abeta40/42 production sharply increased to the plateau level with a relatively small increase in BACE1 expression. Although further increasing BACE1 expression increased beta-secretase activity, it had no additional effect on Abeta production. Furthermore, we found that BACE1 mRNA levels and BACE1 promoter activity were significantly lower than APP mRNA levels and APP promoter activity. Our data demonstrate that lower BACE transcription is responsible for the minority of APP undergoing the amyloidogenic pathway and relatively lower Abeta production in the normal conditions, and that a slight increase in BACE1 can induce a dramatic elevation in Abeta production, indicating that the increase in BACE1 can potentially increase neuritic plaque formation in the pathological condition.
  The FASEB Journal 03/2006; 20(2):285-92. · 5.71 Impact Factor