期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms20030737
关键词
diamine oxidase; histamine; histamine H-3 receptor; histamine N-methyltransferase
资金
- Japan Society for the Promotion of Science (JSPS) [26253016]
- JSPS [18K06886]
- Nishinomiya Basic Research Fund, Japan
- Takeda Science Foundation, Japan
- Grants-in-Aid for Scientific Research [26253016, 18K06886] Funding Source: KAKEN
Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood-brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson's disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据