Role of the APP promoter in Alzheimer's disease: Cell type-specific expression of the β-amyloid precursor protein

Debomoy Lahiri, Yuan Wen Ge

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

One of the major hallmarks in Alzheimer's disease (AD) is amyloid deposition in the brain of afflicted subjects. This tissue-specific deposition of the amyloid β-protein (Aβ) is the major characteristic of AD. Aβ is proteolytically derived from a large Aβ precursor protein (APP). An apparent overexpression of the APP gene in certain areas of the AD brain indicates that abnormalities in gene regulation might be an important factor in AD pathology. The mechanism of expression of APP in different cell types is poorly understood. To understand the contribution of different cell types, such as neuronal, glial, and epithelial cells, APP expression was studied at the message and protein levels. Levels of APP expression, both message and protein, were greater in human neuroblastoma (NB) and PC12 cells than in glial and HeLa cells. DNA transfection experiments suggest that the relative activities of different promoter regions varied according to cell type. Although the upstream regulatory element in the promoter region is necessary for activity in PC12 and HeLa cells, this is not the case for NB cells. A 30-bp proximal promoter region was found to be important for cell type-specific APP gene expression.

Original languageEnglish
Pages (from-to)310-316
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume1030
DOIs
StatePublished - 2004

Fingerprint

Protein Precursors
Amyloid beta-Protein Precursor
Alzheimer Disease
Genetic Promoter Regions
PC12 Cells
Neuroblastoma
HeLa Cells
Gene expression
Neuroglia
Brain
Serum Amyloid A Protein
Proteins
Pathology
Amyloid
Transfection
Protein
Precursor
Cells
Alzheimer's Disease
Epithelial Cells

Keywords

  • β-peptide
  • Aging
  • Brain disorders
  • Dementia
  • Gene regulation
  • Nuclear factor
  • Promoter
  • Tissue specificity
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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abstract = "One of the major hallmarks in Alzheimer's disease (AD) is amyloid deposition in the brain of afflicted subjects. This tissue-specific deposition of the amyloid β-protein (Aβ) is the major characteristic of AD. Aβ is proteolytically derived from a large Aβ precursor protein (APP). An apparent overexpression of the APP gene in certain areas of the AD brain indicates that abnormalities in gene regulation might be an important factor in AD pathology. The mechanism of expression of APP in different cell types is poorly understood. To understand the contribution of different cell types, such as neuronal, glial, and epithelial cells, APP expression was studied at the message and protein levels. Levels of APP expression, both message and protein, were greater in human neuroblastoma (NB) and PC12 cells than in glial and HeLa cells. DNA transfection experiments suggest that the relative activities of different promoter regions varied according to cell type. Although the upstream regulatory element in the promoter region is necessary for activity in PC12 and HeLa cells, this is not the case for NB cells. A 30-bp proximal promoter region was found to be important for cell type-specific APP gene expression.",
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AB - One of the major hallmarks in Alzheimer's disease (AD) is amyloid deposition in the brain of afflicted subjects. This tissue-specific deposition of the amyloid β-protein (Aβ) is the major characteristic of AD. Aβ is proteolytically derived from a large Aβ precursor protein (APP). An apparent overexpression of the APP gene in certain areas of the AD brain indicates that abnormalities in gene regulation might be an important factor in AD pathology. The mechanism of expression of APP in different cell types is poorly understood. To understand the contribution of different cell types, such as neuronal, glial, and epithelial cells, APP expression was studied at the message and protein levels. Levels of APP expression, both message and protein, were greater in human neuroblastoma (NB) and PC12 cells than in glial and HeLa cells. DNA transfection experiments suggest that the relative activities of different promoter regions varied according to cell type. Although the upstream regulatory element in the promoter region is necessary for activity in PC12 and HeLa cells, this is not the case for NB cells. A 30-bp proximal promoter region was found to be important for cell type-specific APP gene expression.

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