Neurotrophic natural products: chemistry and biology

Angew Chem Int Ed Engl. 2014 Jan 20;53(4):956-87. doi: 10.1002/anie.201302268. Epub 2013 Dec 18.

Abstract

Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project.

Keywords: Alzheimer’s disease; dementia; drug discovery; neurodegenerative disease; total synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Humans
  • Molecular Conformation
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Nervous System Diseases / drug therapy*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism

Substances

  • Nerve Growth Factors
  • Small Molecule Libraries