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Exp Neurol. 2010 Sep;225(1):51-4. doi: 10.1016/j.expneurol.2010.04.018. Epub 2010 May 5.

Beyond the signaling effect role of amyloid-ß42 on the processing of APP, and its clinical implications.

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  • 1Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.


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 beta peptide (Abeta) and associated proteins such as beta-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 Abeta activities and suggest potential therapeutic pathways based on their proposed framework of Abeta 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 Abeta'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 Abeta as a transcription factor. Abeta 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.

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