title: Heme oxygenase in neuroprotection: from mechanisms to therapeutic implications.
abstract: Heme oxygenase (HO) was regarded as an enzyme to degrade heme in aging red blood cells; recent studies suggested HO might have other functions such as neuroprotection. HO degrades heme to produce carbon monoxide (CO), iron (Fe²⁺) and biliverdin, which is rapidly converted to bilirubin (BR). Three isoforms of HO were identified in the brain: inducible form (HO-1) and constitutive forms (HO-2 and HO-3). HO-1 and HO-2 may have different mechanisms to protect neurons from oxidative stress. HO-1 is normally barely detectable in the brain. HO-1 can be induced mainly in microglia and astrocytes by oxidative stimulus rapidly. HO-1 might function as an emerging molecule to protect neurons against acute insults mediated by facilitating iron efflux from cells under stress conditions. Up-regulation of HO-1 was also found in brain glial cells in the aging and neurodegenerative diseases. This may lead to iron deposition and oxidative mitochondrial injury. HO-1 may confer neuroprotection or neurotoxic effect because of the balance between beneficial and toxic effects of heme and heme products. Pharmacological modulation of HO-1 induction represents a therapeutic strategy for several nervous system disorders. HO-2 predominantly expressed in neurons. Bilirubin has been demonstrated to protect neurons from oxidative stress in vivo and in vitro. Bilirubin can be oxidized to biliverdin by scavenging peroxyl radicals. HO-2 could protect neurons through bilirubin pathway. HO-2 might also promote neuronal survival through the CO-cGMP-MAPK pathway. Biliverdin/bilirubin may be possible therapeutic candidates to treat nervous system disease related with oxidative damage.
authors: Jijun
authors: J
authors: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D006419:Heme Oxygenase (Decyclizing)