Heme catabolism and heme oxygenase in neurodegenerative disease.
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.
Takeda
Atsushi
A
Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan. atakeda@em.neurol.med.tohoku.ac.jp
Itoyama
Yasuto
Y
Kimpara
Teiko
T
Zhu
Xiongwei
X
Avila
Jesús
J
Dwyer
Barney E
BE
Perry
George
G
Smith
Mark A
MA
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
D007527:Isoenzymes; D016875:tau Proteins; D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)