Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for Alzheimer's disease.

Wanli W. Smith, Myriam Gorospe, John W. Kusiak

Research output: Contribution to journalReview article

Abstract

The accumulation of amyloid beta peptide (Abeta) is believed to be an early and critical event leading to synapse and neuronal cell loss in Alzheimer's Disease (AD). Abeta itself is toxic to neurons in vitro and the load of Abeta in vivo causes the loss of synapses and neurons in brain in animal models. Therefore, there has been considerable interest in elucidating the mechanism(s) of Abeta neurotoxicity. Here, we review the molecular signaling pathways involved in Abeta-induced cell death, including signaling through the neuronal nicotinic receptor and the Abeta-triggered generation of reactive oxygen species (ROS) leading to the activation of the c-jun N-terminal kinase (JNK), and the ensuing phosphorylation of p66Shc and inactivation of the Forkhead transcription factors. This focused review not only provides a better understanding of the signaling mechanisms involved in Abeta-induced cell death, but also underscores the potential of JNK, p66Shc, Forkhead proteins, p25/cdk5, and neuronal nicotinic receptor, as therapeutic targets for AD.

Original languageEnglish (US)
Pages (from-to)355-361
Number of pages7
JournalCNS & neurological disorders drug targets
Volume5
Issue number3
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Fingerprint Dive into the research topics of 'Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for Alzheimer's disease.'. Together they form a unique fingerprint.

  • Cite this