title: Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.
abstract: 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.
authors.affiliation: Section of Pharmacology, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nizzari
authors.forename: Stefano
authors.initials: S
authors.lastname: Thellung
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsaro
authors.forename: Valentina
authors.initials: V
authors.lastname: Villa
authors.forename: Aldo
authors.initials: A
authors.lastname: Pagano
authors.forename: Carola
authors.initials: C
authors.lastname: Porcile
authors.forename: Claudio
authors.initials: C
authors.lastname: Russo
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio