Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets.
Chuhyon CorwinAnastasia NikolopoulouAllen L PanMariela Nunez-SantosShankar VallabhajosulaPeter SerranoJohn BabichPeter A SerranoPublished in: Journal of neuroinflammation (2018)
The PGJ2-induced rat model develops progressive PD pathology, which is a hard-to-mimic aspect of this disorder. Moreover, prevention of most PGJ2-induced PD-like pathology with ibuprofen suggests a positive feedback mechanism between PGJ2 and COX-2 that could lead to chronic neuroinflammation. Notably, this is the first study that analyzes the nigral dopaminergic and microglial distribution and levels of factors of the PGD2/J2 signaling pathway in rodents. Our findings support the notions that upregulation of COX-2 and L-PGDS may be important in the PGJ2 evoked PD-like pathology, and that neuronal DP2 receptor antagonists and L-PGDS inhibitors may be novel pharmacotherapeutics to relieve neuroinflammation-mediated neurodegeneration in PD, circumventing the adverse side effects of cyclooxygenase inhibitors.
Keyphrases
- signaling pathway
- lipopolysaccharide induced
- lps induced
- cerebral ischemia
- high glucose
- traumatic brain injury
- multiple sclerosis
- diabetic rats
- pi k akt
- inflammatory response
- epithelial mesenchymal transition
- drug induced
- cognitive impairment
- endothelial cells
- cell proliferation
- induced apoptosis
- poor prognosis
- subarachnoid hemorrhage
- spinal cord injury
- brain injury
- neuropathic pain
- spinal cord
- stress induced
- endoplasmic reticulum stress