Abstract
NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo. In human clinical trials, NAP has been shown to increase memory scores in patients suffering from amnestic mild cognitive impairment, a precursor to Alzheimers disease and to enhance functional daily behaviors in schizophrenia patients. NAP is derived from activity-dependent neuroprotective protein (ADNP) a molecule that is essential for brain formation, interacting with the chromatin associated protein alpha and the chromatin remodeling complex SWI/SNF and regulating > 400 genes during embryonic development. Partial loss in ADNP results in cognitive deficits and pathology of the microtubule associated protein tau (tauopathy) that is ameliorated in part by NAP replacement therapy. Recent studies increased the scope of NAP neuroprotection and provided further insights into the NAP mechanisms of action. Thus, it has been hypothesized that the presence of tau on axonal microtubules renders them notably less sensitive to the microtubule-severing protein katanin, and NAP was shown to protect microtubules from katanin disruption in the face of reduced tau expression. Parallel studies showed that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. The interaction of these disparate yet complementary pathways is the subject of future studies towards human brain neuroprotection in the clinical scenario.
Keywords: Davunetide, NAP, Drug discovery and development, activity-dependent neuroprotective protein (ADNP), neuroprotection, Alzheimer's disease, Parkinson disease, schizophrenia, cognition, behavior, neurodegeneration, developmental disorders, tau, tauopathy, tubulin, microtubules, progressive supranuclear palsy (PSP), frontotemporal dementia, immune interactions, retina, katanin, glutathione, Kainic acid, wortmannin
Current Pharmaceutical Design
Title: NAP (Davunetide) Provides Functional and Structural Neuroprotection
Volume: 17 Issue: 10
Author(s): Illana Gozes
Affiliation:
Keywords: Davunetide, NAP, Drug discovery and development, activity-dependent neuroprotective protein (ADNP), neuroprotection, Alzheimer's disease, Parkinson disease, schizophrenia, cognition, behavior, neurodegeneration, developmental disorders, tau, tauopathy, tubulin, microtubules, progressive supranuclear palsy (PSP), frontotemporal dementia, immune interactions, retina, katanin, glutathione, Kainic acid, wortmannin
Abstract: NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo. In human clinical trials, NAP has been shown to increase memory scores in patients suffering from amnestic mild cognitive impairment, a precursor to Alzheimers disease and to enhance functional daily behaviors in schizophrenia patients. NAP is derived from activity-dependent neuroprotective protein (ADNP) a molecule that is essential for brain formation, interacting with the chromatin associated protein alpha and the chromatin remodeling complex SWI/SNF and regulating > 400 genes during embryonic development. Partial loss in ADNP results in cognitive deficits and pathology of the microtubule associated protein tau (tauopathy) that is ameliorated in part by NAP replacement therapy. Recent studies increased the scope of NAP neuroprotection and provided further insights into the NAP mechanisms of action. Thus, it has been hypothesized that the presence of tau on axonal microtubules renders them notably less sensitive to the microtubule-severing protein katanin, and NAP was shown to protect microtubules from katanin disruption in the face of reduced tau expression. Parallel studies showed that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. The interaction of these disparate yet complementary pathways is the subject of future studies towards human brain neuroprotection in the clinical scenario.
Export Options
About this article
Cite this article as:
Gozes Illana, NAP (Davunetide) Provides Functional and Structural Neuroprotection, Current Pharmaceutical Design 2011; 17 (10) . https://dx.doi.org/10.2174/138161211795589373
DOI https://dx.doi.org/10.2174/138161211795589373 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pyrazolo-Triazolo-Pyrimidine Derivatives as Adenosine Receptor Antagonists: A Possible Template for Adenosine Receptor Subtypes?
Current Pharmaceutical Design Targeting Neuronal Nicotinic Receptors: a Path to New Therapies
Current Drug Targets - CNS & Neurological Disorders Nimodipine Reappraised: An Old Drug With a Future
Current Neuropharmacology Decreased Expression of Sox-1 in Cerebellum of Rat with Generalized Seizures Induced by Kindling Model
CNS & Neurological Disorders - Drug Targets Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain
Current Neuropharmacology Prader-Willi Syndrome: Genetics, Phenotype, and Management
Current Psychiatry Reviews NMDA Neurotransmission Dysfunction in Behavioral and Psychological Symptoms of Alzheimer's Disease
Current Neuropharmacology Triazino-caffeine Derivatives by Intramolecular Cyclization: Synthesis, Characterization and Antimicrobial Studies
Letters in Organic Chemistry New Glycoside Esters from the Aerial Parts of Artemisia absinthium Linn.
The Natural Products Journal Preface [Hot topic: Carbohydrates (Executive Editor: Istvan Toth)]
Mini-Reviews in Medicinal Chemistry Importance of Zebrafish as an Efficient Research Model for the Screening of Novel Therapeutics in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Involvement of microRNA-146a in the Inflammatory Response of S tatus Epilepticus Rats
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Glutamate Receptors and Related Processes as Drug Targets (Guest Editor: Michel Baudry)]
Current Drug Targets Patented Small Molecules Used for Reprogramming
Recent Patents on Regenerative Medicine Computer-Aided Drug Discovery and Design Targeting Ion Channels
Current Topics in Medicinal Chemistry From A1 to A3 en passant Through A2A Receptors in the Hippocampus: Pharmacological Implications
CNS & Neurological Disorders - Drug Targets RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase
Current Molecular Medicine The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies
Current Neuropharmacology Potassium Channels: Novel Emerging Biomarkers and Targets for Therapy in Cancer
Recent Patents on Anti-Cancer Drug Discovery Astrocyte-Neuron Interaction at Tripartite Synapses
Current Drug Targets