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Query: UNIPROT:P04141 (
granulocyte-macrophage colony-stimulating factor
)
6,790
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Granulocyte-macrophage colony-stimulating factor
(
GM-CSF
) is a hematopoietic cytokine that has the potential for clinical application. The biological effects of
GM-CSF
have been well characterized, and include stimulation of bone marrow hematopoietic stem cell proliferation and inhibition of apoptosis of hematopoietic cells. In contrast, the therapeutic effects of
GM-CSF
on the central nervous system in acute injury such as stroke and spinal cord injury have been reported only recently. To better understand the protective effect of
GM-CSF
on dopaminergic neurons in Parkinson's disease (PD), we investigated the effect of
GM-CSF
on the survival of dopamine neurons and changes in locomotor behavior in a murine PD model. We investigated the neuroprotective effects of
GM-CSF
in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells as well as in embryonic mouse primary mesencephalic neurons (PMNs) in vitro. To investigate the role of
GM-CSF
in vivo, we prepared a mouse
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) PD model, and examined the effects of
GM-CSF
on dopaminergic neuron survival in the substantia nigra and on locomotor behavior. Treatment with
GM-CSF
significantly reduced MPP+-induced dopaminergic cell death in PC12 cells and PMNs in vitro.
GM-CSF
modulated the expression of apoptosis-related proteins, Bcl-2 and Bax, in vitro. Furthermore, administration of
GM-CSF
(50 microg/kg body weight/day) in vivo for 7 days protected dopaminergic neurons in the substantia nigra and improved locomotor behavior in a mouse MPTP model of PD.
...
PMID:Granulocyte-macrophage colony-stimulating factor promotes survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine Parkinson's disease model. 1924 69
Loss of dopaminergic neurons along the nigrostriatal axis, neuroinflammation, and peripheral immune dysfunction are the pathobiological hallmarks of Parkinson's disease (PD).
Granulocyte-macrophage colony-stimulating factor
(
GM-CSF
) has been successfully tested for PD treatment.
GM-CSF
is a known immune modulator that induces regulatory T cells (Tregs) and serves as a neuronal protectant in a broad range of neurodegenerative diseases. Due to its short half-life, limited biodistribution, and potential adverse effects, alternative long-acting treatment schemes are of immediate need. A long-acting mouse
GM-CSF
(mPDM608) was developed through Calibr, a Division of Scripps Research. Following mPDM608 treatment, complete hematologic and chemistry profiles and T-cell phenotypes and functions were determined. Neuroprotective and anti-inflammatory capacities of mPDM608 were assessed in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-intoxicated mice that included transcriptomic immune profiles. Treatment with a single dose of mPDM608 resulted in dose-dependent spleen and white blood cell increases with parallel enhancements in Treg numbers and immunosuppressive function. A shift in CD4
+
T-cell gene expression towards an anti-inflammatory phenotype corresponded with decreased microgliosis and increased dopaminergic neuronal cell survival. mPDM608 elicited a neuroprotective peripheral immune transformation. The observed phenotypic shift and neuroprotective response was greater than observed with recombinant
GM-CSF
(rGM-CSF) suggesting human PDM608 as a candidate for PD treatment.
...
PMID:Neuroprotective Activities of Long-Acting Granulocyte-Macrophage Colony-Stimulating Factor (mPDM608) in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Intoxicated Mice. 3263 17
