Neurodegeneration in Alzheimer disease: Role of amyloid precursor protein and presenilin 1 intracellular signaling

Mario Nizzari, Stefano Thellung, Alessandro Corsaro, Valentina Villa, Aldo Pagano, Carola Porcile, Claudio Russo, Tullio Florio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number187297
JournalJournal of Toxicology
Volume2012
DOIs
Publication statusPublished - 2012

Fingerprint

Presenilin-1
Amyloid beta-Protein Precursor
Alzheimer Disease
Amyloid
Presenilin-2
Cell signaling
tau Proteins
Signal transduction
Neurofibrillary Tangles
Amyloid Plaques
Complex networks
Neurodegenerative Diseases
Synapses
Neurons
Signal Transduction
Cell Cycle
Cells
Mutation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Neurodegeneration in Alzheimer disease : Role of amyloid precursor protein and presenilin 1 intracellular signaling. / Nizzari, Mario; Thellung, Stefano; Corsaro, Alessandro; Villa, Valentina; Pagano, Aldo; Porcile, Carola; Russo, Claudio; Florio, Tullio.

In: Journal of Toxicology, Vol. 2012, 187297, 2012.

Research output: Contribution to journalArticle

Nizzari, Mario ; Thellung, Stefano ; Corsaro, Alessandro ; Villa, Valentina ; Pagano, Aldo ; Porcile, Carola ; Russo, Claudio ; Florio, Tullio. / Neurodegeneration in Alzheimer disease : Role of amyloid precursor protein and presenilin 1 intracellular signaling. In: Journal of Toxicology. 2012 ; Vol. 2012.
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