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Titolo:
Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons
Autore:
Guo, X; Dawson, VL; Dawson, TM;
Indirizzi:
Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 Neurol, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 urosci, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 hysiol, Baltimore, MD 21287 USA
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 9, volume: 13, anno: 2001,
pagine: 1683 - 1693
SICI:
0953-816X(200105)13:9<1683:NLENAN>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; FK506 BINDING-PROTEIN; IN-VIVO; IMMUNOPHILIN LIGANDS; MOLECULAR-CLONING; NEURITE OUTGROWTH; CELL-DEATH; IMMUNOSUPPRESSIVE DRUGS; NEUROTROPHIC ACTIONS; PHOSPHATASE-ACTIVITY;
Keywords:
6-OHDA; FKBP; immunophilin; mouse; MPP+; rat; tyrosine hydroxylase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Dawson, TM Johns Hopkins Univ, Sch Med, Dept Neurol, 600 N Wolfe St,Carnegie 2-214, Baltimore, MD 21287 USA Johns Hopkins Univ 600 N Wolfe St,Carnegie 2-214 Baltimore MD USA 21287
Citazione:
X. Guo et al., "Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons", EUR J NEURO, 13(9), 2001, pp. 1683-1693

Abstract

Immunosuppressant drugs, like FK506, and nonimmunosuppressant compounds like, GPI1046 and L685818, are immunophilin ligands that specifically bind toimmunophilins, 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, weuse 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 mum 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 theretraction and loss of neuronal processes, while FK506, GPI1046 and L685818 promote regeneration of these processes as indicated by increases in process number and length. To examine if FKBP12 is required for neurotrophic effects of immunophilin ligands, we cultured dopaminergic neurons from FKBP12knockout mice and find that FK506 still protects dopaminergic neurons against MPP+ toxicity. These results suggest that FKBP12 is not essential for the neurotrophic properties of immunophilin ligands, and immunophilin ligands are a new class of neuroprotective and neuroregenerative agents that may have therapeutic potential in a variety of neurological disorders.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 01:40:10