Heme oxygenase-1 as a therapeutic target in neurodegenerative diseases and brain infections.
Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to generate carbon monoxide, biliverdin and free iron. Increased HO-1 levels constitute an anatomopathological feature of many neurological diseases, such as neurodegenerative disorders and brain infections, which correlate with exacerbated oxidative stress and inflammation. It is generally accepted that the elevated HO-1 levels represent an attempt to restore redox homeostasis and to down-modulate inflammation. However, experimental observations indicate that the extent of HO-1 induction may be critical because excessive heme degradation may result in toxic levels of CO, bilirubin and, more importantly, iron. Pharmacological modulation of HO-1 levels in the brain, within therapeutic limits, shows promising results in models of Alzheimer's (AD), Parkinson's (PD) and of infectious diseases, such as malaria. A more complete understanding on how HO-1 is involved in the pathogenesis of neurological diseases will be essential to develop therapeutic approaches. In the next coming years we will witness the description of chemicals, drugs or dietary products that cross the blood brain barrier efficiently, activate HO-1 expression, and achieve neuroprotective and anti-inflammatory effects in vivo.
Cuadrado
Antonio
A
Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols, Facultad de Medicina, Madrid, Spain. antonio.cuadrado@uam.es
Rojo
Ana I
AI
D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D001664:Biliverdine / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D002248:Carbon Monoxide / Q000378:metabolism; D002494:Central Nervous System Infections / Q000188:drug therapy* / Q000201:enzymology; D004660:Encephalitis / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D009103:Multiple Sclerosis / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000201:enzymology
D002248:Carbon Monoxide; D007501:Iron; D051547:Heme Oxygenase-1; D001664:Biliverdine