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, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)438-449
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume323
Issue number2
DOIs
StatePublished - Nov 2007

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