|
| CNS disorder | PPARδ agonist | Neuroprotective benefits |
|
| Stroke |
GW501516 | Significantly attenuated the cortical infarct area following MCAO-induced ischemic damage in rats [12] |
| Reduced OGD-induced MMP-9 enzymatic activity in mice [13] |
| Protected against vascular endothelial cell death by inhibiting expression of miR-15a, which increased Bcl-2 expression, reduced golgi fragmentation, and decreased caspase-3 activity [43] |
| L-165041 | Significantly attenuated the cortical infarct area following MCAO-induced ischemic damage in rats [12] |
|
| Multiple sclerosis | GW0742 | Reduced emergence of new cortical lesions, increased PLP mRNA, and reduced IL-1β expression in mice immunized with MOG [14] |
|
GW501516 | Reduced IL-1, IL-23, IFNγ, and IL-17 and increased IL-4 and IL-10 in mice immunized with MOG [50] |
| Reduced LPS-induced TNF-α and iNOS mRNA in aggregating brain cells [54] |
| L-165041 | Reduced IL-1, IL-23, IFNγ, and IL-17 and increased IL-4 and IL-10 in mice immunized with MOG [50] |
|
| Alzheimer’s disease |
GW0742 | Blocked Aβ peptide-induced cell death, as measured by LDH release and Fluorojade B staining, in primary cultures of rat cortical neurons [21] |
| Decreased amyloid burden, increased neprilysin expression, and decreased GFAP expression in 5xFAD mice [22] |
| L-160,043 | Prevented STZ-induced neurodegeneration and cognitive impairment in rats. This was associated with reduced tau phosphorylation, increased choline acetyltransferase, attenuated 8-OHdG and HNE, and reduced GFAP expression [15] |
|
| Parkinson’s disease |
GW501516 | Ameliorated MPTP-induced depletion of striatal dopamine and its metabolites in mice [12] |
| Reduced Caspase-3 and protected SH-SY5Y cells from MPP+-induced cell death [12] |
|
L-165041 | Ameliorated MPTP-induced depletion of striatal dopamine and its metabolites in mice [12] |
| Reduced Caspase-3 and protected SH-SY5Y cells from MPP+-induced cell death [12] |
|
| Radiation-induced brain injury | GW0742 | Prevented microglial activation (CD68+ cells) in mice irradiated with a single dose of 10 Gy (unpublished) |
| L-165041 | Prevented intracellular ROS generation, Cox-2, iNOS, and MCP-1 expression, IL-1β and TNF-α mRNA, and NF-κB, and AP-1 activation in BV-2 cells irradiated with 10 Gy (unpublished) |
|
| Spinal cord injury |
GW0742 | Improved motor function of mice and reduced TNF-α, IL-1β, and iNOS expression, NF-κB activation, neutrophil infiltration, nitrotyrosine and lipid peroxidation, FasL expression, and TUNEL staining [23] |
| Reduced Cox-2, p-p38 MAPK, and p-c-jun expression, and NF-κB activation in murine spinal cord slices [88] |
|
