Back to Search
Start Over
Peroxisome proliferator-activated receptor-γ (PPARγ) agonist is neuroprotective and stimulates PGC-1α expression and CREB phosphorylation in human dopaminergic neurons
- Source :
- Neuropharmacology. 102
- Publication Year :
- 2015
-
Abstract
- Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H2O2 and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1α. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPARγ agonist GW1929 influences CREB signaling and PGC-1α activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPARγ-PGC-1α signaling in neurons may have beneficial effects in PD and possible also in other brain disorders.
- Subjects :
- 0301 basic medicine
Agonist
medicine.medical_specialty
medicine.drug_class
Peroxisome proliferator-activated receptor
Mitochondrion
Biology
CREB
Neuroprotection
Cell Line
03 medical and health sciences
Cellular and Molecular Neuroscience
Benzophenones
0302 clinical medicine
Sirtuin 1
Internal medicine
medicine
Humans
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Pharmacology
chemistry.chemical_classification
Organelle Biogenesis
Dopaminergic Neurons
Dopaminergic
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Cell biology
Mitochondria
PPAR gamma
030104 developmental biology
Endocrinology
Neuroprotective Agents
chemistry
Mitochondrial biogenesis
biology.protein
Tyrosine
Organelle biogenesis
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 18737064
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....9179b8e46bd78f453aac5cea6385bd26