Signaling Mechanisms Underlying Aβ Toxicity: Potential Therapeutic Targets for Alzheimers Disease

Author(s): Wanli W. Smith, Myriam Gorospe, John W. Kusiak.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 5 , Issue 3 , 2006

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The accumulation of amyloid β peptide (Aβ) is believed to be an early and critical event leading to synapse and neuronal cell loss in Alzheimers Disease (AD). Aβ itself is toxic to neurons in vitro and the load of Aβ 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 Aβ neurotoxicity. Here, we review the molecular signaling pathways involved in Aβ-induced cell death, including signaling through the neuronal nicotinic receptor and the Aβ-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 Aβ-induced cell death, but also underscores the potential of JNK, p66Shc, Forkhead proteins, p25/cdk5, and neuronal nicotinic receptor, as therapeutic targets for AD.

Keywords: JNK, p66Shc, Forkhead proteins, cdk5, apoptosis, phosphorylation, reactive oxygen species, neuronal nicotinic receptor

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Article Details

Year: 2006
Page: [355 - 361]
Pages: 7
DOI: 10.2174/187152706784111515
Price: $58

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