Beyond the signaling effect role of amyloid-β42 on the processing of APP, and its clinical implications

Debomoy K. Lahiri, Bryan Maloney

Research output: Contribution to journalComment/debate

30 Scopus citations

Abstract

Alzheimer's disease (AD) currently has over 6. million victims in the USA, alone. The recently FDA approved drugs for AD only provide mild, transient relief for symptoms without addressing underlying mechanisms to a significant extent. Basic understanding of the activities of the amyloid β peptide (Aβ) and associated proteins such as β-site APP-cleaving enzyme 1 (BACE1) is necessary to develop effective medical responses to AD. Recently (Exper. Neurol. 2010. 221, 18-25), Tabaton et al. have presented a model of both non-pathological and pathological Aβ activities and suggest potential therapeutic pathways based on their proposed framework of Aβ acting as the signal that induces a kinase cascade, ultimately stimulating transcription factors that upregulate genes such as BACE1. We respond by presenting evidence of Aβ's other activities, including protection against metal-induced reactive oxidizing species (ROS), modification of cholesterol transport, and potential activity as a transcription factor in its own right. We touch upon clinical implications of each of these functions and highlight the currently unexplored implications of our suggested novel function of Aβ as a transcription factor. Aβ appears to be a highly multi-functional peptide, and any or all of the pathways it engages in is a likely candidate for antiAD drug development.

Original languageEnglish (US)
Pages (from-to)51-54
Number of pages4
JournalExperimental Neurology
Volume225
Issue number1
DOIs
StatePublished - Sep 1 2010

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Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid beta peptide
  • Clinical trial
  • Dementia
  • Drug discovery
  • Gene regulation
  • Molecular pharmacology
  • Signaling
  • Transcription factor
  • Treatment

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

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