RT Journal Article
SR Electronic
T1 Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 438
OP 449
DO 10.1124/jpet.107.129551
VO 323
IS 2
A1 Inna Vulih-Shultzman
A1 Albert Pinhasov
A1 Shmuel Mandel
A1 Nikolaos Grigoriadis
A1 Olga Touloumi
A1 Zipora Pittel
A1 Illana Gozes
YR 2007
UL http://jpet.aspetjournals.org/content/323/2/438.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics