A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

Abstract

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

• Authors: Qi Chen, Marguerite Prior, Richard Dargusch, Amanda Roberts, Roland Riek, Cédric Eichmann, Chandramouli Chiruta, Tatsuhiro Akaishi, Kazuho Abe, Pamela Maher, David Schubert
• Journal: PloS one (PLoS One) Vol. 6 Issue 12 Pg. e27865 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22194796 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Brain-Derived Neurotrophic Factor
• CNB 001
• Heat-Shock Proteins
• Nerve Growth Factors
• Neuroprotective Agents
• Oxidants
• Pyrazoles
• Curcumin

Topics

• Alzheimer Disease (drug therapy, metabolism, pathology, physiopathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Behavior, Animal (drug effects)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cognition (drug effects)
• Curcumin (analogs & derivatives, chemistry, pharmacology)
• Disease Models, Animal
• Heat-Shock Proteins (metabolism)
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Immunohistochemistry
• Inflammation (pathology)
• Long-Term Potentiation (drug effects)
• Memory (drug effects)
• Mice
• Nerve Growth Factors (pharmacology)
• Neuroprotective Agents (chemistry, pharmacology)
• Oxidants (metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Pyrazoles (chemistry, pharmacology)
• Rats
• Solubility (drug effects)
• Structure-Activity Relationship
• Synapses (drug effects, metabolism)
• Up-Regulation (drug effects)