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Journal of Toxicology
Volume 2012, Article ID 187297, 13 pages
Review Article

Neurodegeneration in Alzheimer Disease: Role of Amyloid Precursor Protein and Presenilin 1 Intracellular Signaling

1Section of Pharmacology, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy
2IRCCS Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), Università di Genova, 16132 Genova, Italy
3Department of Health Sciences, University of Molise, 86100 Campobasso, Italy

Received 26 July 2011; Revised 14 October 2011; Accepted 26 October 2011

Academic Editor: Wei Zheng

Copyright © 2012 Mario Nizzari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.