HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 21, 99914, May 26, 2006

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?

Brain Therapy

Animals administered an FKBP38-specific inhibitor (N-(N',N'-dimethylcarboxamidomethyl)cycloheximide (DM-CHX)) exhibited neurogenesis.

The immunosuppressive drug FK506 reversibly inhibits members of the FK506-binding protein (FKBP) family of peptidylprolyl cis/trans-isomerases. Interestingly, FK506 and its open chain derivatives also demonstrate neuroprotective and neuroregenerative effects in a wide range of animal models mimicking Parkinson disease, dementia, stroke, and nerve damage. However, the molecular mechanism of these FK506-mediated effects remains elusive.

Now, Frank Edlich and colleagues shed some light on this issue by showing that these neurotrophic FKBP ligands specifically target FKBP38. This isomerase is different from the other members of the FKBP family in that it is only active when bound to calmodulin/Ca²⁺. Edlich et al. synthesized an FKBP38-specific inhibitor and used it in a rat model of transient focal cerebral ischemia. They found that the ligand caused neuronal protection as well as neural stem cell proliferation and neuronal differentiation. Diseased animals with sustained motor behavior deficits also showed improvement when administered the drug, hinting at its potential therapeutic application. Not only does this manuscript present a beautiful synthesis of biochemistry, molecular pharmacology, and experimental medicine, it also provides a possible strategy for the treatment of acute and/or chronic neurodegenerative diseases.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 14961-14970

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?