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Neuroimmunophilin Ligands Exert Neuroregeneration and Neuroprotection in Midbrain Dopaminergic Neurons by Xin Guo; Valina L. Dawson; Ted M. Dawson is a Neuroscience article available to read on EtoBox.

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## Abstract Immunosuppressant drugs, like FK506, and nonimmunosuppressant compounds like, GPI1046 and L685818, are immunophilin ligands that specifically bind to immunophilins, like FK506 binding protein 12 (FKBP12). Several lines of evidence show that these ligands exert neurotrophic properties in neural injury models and in PC12 cells. However, the mechanism of the neurotrophic function of the immunophilin ligands is poorly known. In the present study, we use MPP^+^ and 6‐OHDA toxicity models to examine both neuroprotective and neuroregenerative effects of immunophilin ligands on primary cultures of midbrain dopaminergic neurons. We find that FK506, GPI1046 and L685818 at concentrations from 0.01 to 1 μm partially, but significantly, protect dopaminergic neurons against both MPP^+^ and 6‐OHDA toxicity. By Western blot analysis, we also find that all three compounds prevent tyrosine hydroxylase (TH) loss induced by MPP^+^ and 6‐OHDA treatments. Morphologic analysis of dopaminergic neurons, by immunocytochemistry, shows that MPP^+^ and 6‐OHDA cause the retraction and loss of neuronal processes, while FK506, GPI1046 and L685818 promote regeneration of these processes as indicated by

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Author

Xin Guo; Valina L. Dawson; Ted M. Dawson

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0953-816X)

Published

2001

Language

EN

Field

Neuroscience (Life Sciences)