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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 24, 2007; DOI: 10.1124/jpet.107.129551

0022-3565/07/3232-438-449$20.00
JPET 323:438-449, 2007
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NEUROPHARMACOLOGY

Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model

Inna Vulih-Shultzman, Albert Pinhasov, Shmuel Mandel, Nikolaos Grigoriadis, Olga Touloumi, Zipora Pittel, and Illana Gozes

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (I.V.-S., A.P., S.M., Z.P., I.G.); and Department of Neurology and Laboratory of Experimental Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece (N.G., O.T.)

Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate essential genes. Because complete ADNP deficiency is embryonic lethal, the outcome of partial ADNP deficiency was examined. ADNP+/– mice exhibited cognitive deficits, significant increases in phosphorylated tau, tangle-like structures, and neurodegeneration compared with ADNP+/+ mice. Increased tau hyperphosphorylation is known to cause memory impairments in neurodegenerative diseases associated with tauopathies, including the most prevalent Alzheimer's disease. The current results suggest that ADNP is an essential protein for brain function and plays a role in normal cognitive performance. ADNP-deficient mice offer an ideal paradigm for evaluation of cognitive enhancers. NAP (NAPVSIPQ) is a peptide derived from ADNP that interacts with microtubules and provides potent neuroprotection. NAP treatment partially ameliorated cognitive deficits and reduced tau hyperphosphorylation in the ADNP+/– mice. NAP is currently in phase II clinical trials assessing effects on mild cognitive impairment.

Received August 2, 2007; accepted August 23, 2007.

Address correspondence to: Illana Gozes, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. E-mail: igozes{at}post.tau.ac.il




This article has been cited by other articles:


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A Neuronal Microtubule-Interacting Agent, NAPVSIPQ, Reduces Tau Pathology and Enhances Cognitive Function in a Mouse Model of Alzheimer's Disease
J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 146 - 153.
[Abstract] [Full Text] [PDF]


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