Taking down the unindicted co-conspirators of amyloid β- peptide-mediated neuronal death

Shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors

Debomoy Lahiri, Yuan Wen Ge, Jack T. Rogers, Kumar Sambamurti, Nigel H. Greig, Bryan Maloney

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Major hallmarks of Alzheimer's disease (AD) include brain deposition of the amyloid-β peptide (Aβ), which is proteolytically cleaved from a large Aβ precursor protein (APP) by β and γ- secretases. A transmembrane aspartyl protease, β-APP cleaving enzyme (BACE1), has been recognized as the β-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5′-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated region (UTR) contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalCurrent Alzheimer Research
Volume3
Issue number5
DOIs
StatePublished - Dec 2006

Fingerprint

YY1 Transcription Factor
Protein Precursors
Amyloid
Transcription Factors
Amyloid Precursor Protein Secretases
Peptides
5' Flanking Region
Genes
Alzheimer Disease
Proteins
Aspartic Acid Proteases
Neuronal Plasticity
Initiator Codon
5' Untranslated Regions
Transcription Factor AP-1
Reporter Genes
Genetic Promoter Regions
Oxidative Stress
Binding Sites
Apoptosis

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Taking down the unindicted co-conspirators of amyloid β- peptide-mediated neuronal death : Shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors. / Lahiri, Debomoy; Ge, Yuan Wen; Rogers, Jack T.; Sambamurti, Kumar; Greig, Nigel H.; Maloney, Bryan.

In: Current Alzheimer Research, Vol. 3, No. 5, 12.2006, p. 475-483.

Research output: Contribution to journalArticle

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