Article

Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model.

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Journal of Pharmacology and Experimental Therapeutics (impact factor: 3.83). 12/2007; 323(2):438-49. DOI:10.1124/jpet.107.129551 pp.438-49
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
35 Views
  • Source
    Article: Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy.
    Michael Gold, Stefan Lorenzl, Alistair J Stewart, Bruce H Morimoto, David R Williams, Illana Gozes
    [show abstract] [hide abstract]
    ABSTRACT: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.
    Neuropsychiatric Disease and Treatment 01/2012; 8:85-93. · 1.81 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Activity-dependent neuroprotective protein
 
brain function
 
cause memory impairments
 
cognitive enhancers
 
current results
 
essential genes
 
ideal paradigm
 
interacts
 
mild cognitive impairment
 
NAPVSIPQ
 
neurodegenerative diseases
 
normal cognitive performance
 
phase II clinical trials
 
phosphorylated tau
 
potent neuroprotection
 
prevalent Alzheimer's disease