Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurobiol Dis. 1998 Aug;5(2):97-106.

A novel immunophilin ligand: distinct branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of Parkinson's disease.

Author information

  • 1Neuroregeneration Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02178, USA. Costanti@helix.mgh.harvard.edu

Abstract

Protection or regeneration of the dopaminergic (DA) system would be of significant therapeutic value for Parkinson's disease. Immunophilin ligands, such as FK506, can produce neurotrophic effects in vitro and in vivo, but their immunosuppressive effects make them unsuitable for neurological application. This study demonstrates that a novel, nonimmunosuppressive immunophilin ligand (V-10,367) increased the number of neurites extended by tyrosine hydroxylase positive (TH+) DA neurons in embryonic day 14 primary DA neuronal cultures. In contrast, the immunosuppressive immunophilin ligand FK506 increased the length of TH+ neurites. After oral administration in MPTP-treated mice, V-10,367 completely protected against MPTP-induced loss of striatal TH+ axonal density, while FK506 did not. These experiments demonstrate that nonimmunosuppressive immunophilin ligands specifically increase neurite branching in primary DA neuronal culture and possess neurotrophic actions in vivo with potential application to neurodegenerative disease.

PMID:
9746907
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk