title: Heme catabolism and heme oxygenase in neurodegenerative disease.
abstract: Heme oxygenase, the rate-limiting step in heme catabolism, appears to play an important role in a number of neurodegenerative disorders, such as Alzheimer disease. Interestingly, the spatial distribution of heme oxygenase-1 expression in diseased brain is essentially identical to that of the pathological expression of tau, suggesting a key role for both in disease progression. Like heme oxygenase, the expression, phosphorylation, and aggregation of tau are regulated through signal cascades, including the extracellular signal-regulated kinases, whose activities are modulated by oxidative stress. Therefore, the expression of tau and heme oxygenase-1 in a coordinated manner likely plays a pivotal role in the cytoprotection of neuronal cells. This places heme oxygenase at the center of disease pathogenesis and offers a novel therapeutic approach targeted at either the causes or consequences of enzyme induction.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan. atakeda@em.neurol.med.tohoku.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Teiko
authors.initials: T
authors.lastname: Kimpara
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Barney E
authors.initials: BE
authors.lastname: Dwyer
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D016875:tau Proteins; D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)