Brain hydrogen sulfide is severely decreased in Alzheimer's disease.
Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H2S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.
Eto
Ko
K
National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan.
Asada
Takashi
T
Arima
Kunimasa
K
Makifuchi
Takao
T
Kimura
Hideo
H
D000544:Alzheimer Disease / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000737:chemistry; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism
D000596:Amino Acids; D006710:Homocysteine; D012436:S-Adenosylmethionine; D003545:Cysteine; D006862:Hydrogen Sulfide