title: A cellular model of amyloid precursor protein processing and amyloid-β peptide production.
abstract: BACKGROUND
  A hallmark pathologic feature of Alzheimer's disease (AD) is accumulation of neuritic senile plaques in the brain parenchyma. Neurotoxic plaque cores are composed predominantly of amyloid-β (Aβ) peptides of 40 and 42 amino acids in length, formed by sequential cleavage of amyloid precursor protein (APP) by β-, and γ-secretases. There is a great interest in approaches to modulate Aβ peptide production and develop therapeutic interventions to reduce Aβ levels to halt or slow the progression of neurodegeneration.
  
  
  METHODS
  We characterized and present the BE(2)-M17 human neuroblastoma cell line as a novel in vitro model of the APP-cleavage cascade to support future (1) functional studies of molecular regulators in Aβ production, and (2) high-throughput screening assays of new pharmacotherapeutics.
  
  
  RESULTS
  In BE(2)-M17 cells, both RNA (i.e., RT-PCR, RNA sequencing) and protein analyses (i.e., Western blots, ELISA), show endogenous expression of critical components of the amyloidogenic pathway, APP-cleavage intermediates CTF83 and CTF99, and final cleavage products Aβ40 and Aβ42. We further report effects of retinoic acid-mediated differentiation on morphology and gene expression in this cell line.
  
  
  CONCLUSIONS
  In contrast to primary isolates or other cell lines reported in current literature, BE(2)-M17 not only sustains baseline expression of the full contingent of APP-processing components, but also remains stably adherent during culture, facilitating experimental manipulations.
  
  
  CONCLUSIONS
  Our evidence supports the use of BE(2)-M17 as a novel, human, cell-based model of the APP processing pathway that offers a potential streamlined approach to dissect molecular functions of endogenous regulatory pathways, and perform mechanistic studies to identify modulators of Aβ production.
authors: Haldeman Laboratory of Molecular Diagnostics and Therapeutics, Banner Sun Health Research Institute, 10515 W, Santa Fe Drive, Sun City, AZ 85351, USA. Electronic address: mimi.macias@bannerhealth.com.
authors: Mimi P
authors: MP
authors: Macias
authors: Haldeman Laboratory of Molecular Diagnostics and Therapeutics, Banner Sun Health Research Institute, 10515 W, Santa Fe Drive, Sun City, AZ 85351, USA. Electronic address: amanda.gonzales@bannerhealth.com.
authors: Amanda M
authors: AM
authors: Gonzales
authors: Neurogenomics Division, The Translational Genomics Research Institute, 445N, Fifth Street, Phoenix, AZ 85004, USA. Electronic address: asiniard@tgen.org.
authors: Ashley L
authors: AL
authors: Siniard
authors: Haldeman Laboratory of Molecular Diagnostics and Therapeutics, Banner Sun Health Research Institute, 10515 W, Santa Fe Drive, Sun City, AZ 85351, USA. Electronic address: aaron.walker@bannerhealth.com.
authors: Aaron W
authors: AW
authors: Walker
authors: Neurogenomics Division, The Translational Genomics Research Institute, 445N, Fifth Street, Phoenix, AZ 85004, USA. Electronic address: jcorneveaux@tgen.org.
authors: Jason J
authors: JJ
authors: Corneveaux
authors: Neurogenomics Division, The Translational Genomics Research Institute, 445N, Fifth Street, Phoenix, AZ 85004, USA. Electronic address: mhuentelman@tgen.org.
authors: Matthew J
authors: MJ
authors: Huentelman
authors: Haldeman Laboratory of Molecular Diagnostics and Therapeutics, Banner Sun Health Research Institute, 10515 W, Santa Fe Drive, Sun City, AZ 85351, USA. Electronic address: marwan.sabbagh@bannerhealth.com.
authors: Marwan N
authors: MN
authors: Sabbagh
authors: Haldeman Laboratory of Molecular Diagnostics and Therapeutics, Banner Sun Health Research Institute, 10515 W, Santa Fe Drive, Sun City, AZ 85351, USA. Electronic address: boris.decourt@bannerhealth.com.
authors: Boris
authors: B
authors: Decourt
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007641:Keratolytic Agents / Q000494:pharmacology; D008954:Models, Biological; D009447:Neuroblastoma / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007641:Keratolytic Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; D014212:Tretinoin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer's; Amyloid-beta; BE(2)-M17; In vitro; Secretase; TNF