| | Tissue
Distribution | PPAR Agonists | Effect and Mode
of Action in CNS diseases |
| PPAR α
Expressed in liver, heart, kidney, large
intestine, skeletal muscle and astrocytes. PPARα knockout mice develop severe LPS-induced
inflammation | Palmitic
acid, linoleic acid, stearic acid, palmitoleic acid, oleic acid, 8-HETE,
Wy-14643, clofibrate, nafenopin, bezafibrate, fenofibrate | PPARα agonists
inhibit Aβ induced expression
of TNFα, IL-6, IL-4
and infiltration of CD4+ T cells in the CNS of AD; reduce ICAM-1
expression and oxidative damage in stroke; protect MPTP-induced loss of
neurons in PD; protect mice from EAE by inhibiting IFNγ, TNFα and IL-6
production in stroke, cerebral ischemia and MS models | PPAR β/δ
Expressed ubiquitously in brain, adipose
tissue and skin. PPARβ/δ knockout mice show reduced fat deposition
| Prostacyclin,
PGI2, GW0742, GW501516, GW7842, L165041 | PPARβ/δ agonists reduce the severity of EAE and stroke by inhibiting NF-κB and Jak-Stat
signaling pathways in immune cells from MS and stroke models | PPAR γ
Expressed in heart, muscle, colon, kidney, pancreas, spleen, macrophage,
intestine, adipose tissue and liver.
PPARγ knockouts are
embryonically lethal | Prostaglandin
J2, thiazolidinediones, pioglitazone,
rosiglitazone, GW78456, WY14,643, GW7647 | PPARγ agonists inhibit
T-cell proliferation, IFNγ, IL-10 and IL-4 production through blocking NF-κB,
AP-1 and Jak-Stat pathways in CNS diseases models of AD, PD, Trauma, MS, ALS,
stroke and ischemia |
|
|
