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Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists.

Bernardo A, Minghetti L - PPAR Res (2008)

Bottom Line: In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders.PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies.The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.

ABSTRACT
In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-gamma agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation.

No MeSH data available.


Related in: MedlinePlus

Cellular targets of PPAR-γ agonists in neurodegenerative diseases. PPAR-γagonists can control neuroinflammation, neurodegeneration, and demyelination byeffecting several cellular targets and by several direct and indirectmechanisms. PPAR-γ agonists can control glial activation, preventing a number of proinflammatoryactivities that can contribute to myelin/OL damage and neurotoxicity PPAR-γagonists may also affect OLs and neurons, by preventing release inflammatorymediators and/or promote the synthesis of soluble factors or membrane-boundmolecules that control glial activation.
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Related In: Results  -  Collection


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fig1: Cellular targets of PPAR-γ agonists in neurodegenerative diseases. PPAR-γagonists can control neuroinflammation, neurodegeneration, and demyelination byeffecting several cellular targets and by several direct and indirectmechanisms. PPAR-γ agonists can control glial activation, preventing a number of proinflammatoryactivities that can contribute to myelin/OL damage and neurotoxicity PPAR-γagonists may also affect OLs and neurons, by preventing release inflammatorymediators and/or promote the synthesis of soluble factors or membrane-boundmolecules that control glial activation.

Mentions: The beneficial effects of PPAR-γ agonists indegenerative, inflammatory and traumatic brain pathologies are most likelymediated by several mechanisms, which may be disease-specific and involve bothperipheral and central anti-inflammatory activities, by affecting crucialfunctions of peripheral (macrophages and/or lymphocytes) and central (microglialcells) immune cells. Besides microglia, PPAR-γ agonists can act on other neuralcell types, including astrocytes, neurons, and oligodendrocytes (Figure 1).


Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists.

Bernardo A, Minghetti L - PPAR Res (2008)

Cellular targets of PPAR-γ agonists in neurodegenerative diseases. PPAR-γagonists can control neuroinflammation, neurodegeneration, and demyelination byeffecting several cellular targets and by several direct and indirectmechanisms. PPAR-γ agonists can control glial activation, preventing a number of proinflammatoryactivities that can contribute to myelin/OL damage and neurotoxicity PPAR-γagonists may also affect OLs and neurons, by preventing release inflammatorymediators and/or promote the synthesis of soluble factors or membrane-boundmolecules that control glial activation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2367430&req=5

fig1: Cellular targets of PPAR-γ agonists in neurodegenerative diseases. PPAR-γagonists can control neuroinflammation, neurodegeneration, and demyelination byeffecting several cellular targets and by several direct and indirectmechanisms. PPAR-γ agonists can control glial activation, preventing a number of proinflammatoryactivities that can contribute to myelin/OL damage and neurotoxicity PPAR-γagonists may also affect OLs and neurons, by preventing release inflammatorymediators and/or promote the synthesis of soluble factors or membrane-boundmolecules that control glial activation.
Mentions: The beneficial effects of PPAR-γ agonists indegenerative, inflammatory and traumatic brain pathologies are most likelymediated by several mechanisms, which may be disease-specific and involve bothperipheral and central anti-inflammatory activities, by affecting crucialfunctions of peripheral (macrophages and/or lymphocytes) and central (microglialcells) immune cells. Besides microglia, PPAR-γ agonists can act on other neuralcell types, including astrocytes, neurons, and oligodendrocytes (Figure 1).

Bottom Line: In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders.PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies.The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.

ABSTRACT
In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-gamma agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation.

No MeSH data available.


Related in: MedlinePlus