PPAR-gamma: therapeutic target for ischemic stroke.
The peroxisome proliferator activated receptors (PPARs), which belong to the nuclear receptor superfamily, are key regulators of glucose and fat metabolism. The PPAR-gamma isoform is involved in the regulation of cellular glucose uptake, protection against atherosclerosis and control of immune reactions. In addition, the activation of PPAR-gamma effectively attenuates neurodegenerative and inflammatory processes in the brain. Here, we review a novel aspect of beneficial and clinically relevant PPAR-gamma actions: neuroprotection against ischemic injury mediated by intracerebral PPAR-gamma, which is expressed in neurons and microglia. Together with the recent observation that the PPAR-gamma ligand pioglitazone reduces the incidence of stroke in patients with type 2 diabetes, this review supports the concept that activators of PPAR-gamma are effective drugs against ischemic injury.
Culman
Juraj
J
Institute of Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Hospitalstrasse 4, 24105 Kiel, Germany.
Zhao
Yi
Y
Gohlke
Peter
P
Herdegen
Thomas
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone