2020 Fiscal Year Final Research Report
Expression study of molecules in the proline metabolic pathway in the postmortem brain of patients with schizophrenia
Project/Area Number |
19K23948
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0902:General internal medicine and related fields
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Research Institution | Fukushima Medical University |
Principal Investigator |
Nagaoka Atsuko 福島県立医科大学, 医学部, 助教 (20844632)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | 統合失調症 / 死後脳 / プロリダーゼ / P5Cシンセターゼ / プロリン / ALDH4A1 / PEPD / ALDH18A1 |
Outline of Final Research Achievements |
We have been analyzing the relationship between protein expression and gene polymorphisms (single-nucleotide polymorphisms [SNPs]) in the postmortem brains of patients with schizophrenia. We found that Aldehyde dehydrogenase 4 family member A1 (ALDH4A1), an enzyme in the pathway that metabolizes proline to glutamate, was significantly increased in the postmortem brains of patients with schizophrenia. In this study, in order to elucidate the molecular mechanisms underlying schizophrenia, we measured the protein expression levels of P5C synthase and prolidase in the postmortem brain, which are encoded by genes (ALDH18A1, PEPD) with three SNPs that correlate with ALDH4A1 expression levels.We have published one related paper.
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Free Research Field |
精神疾患死後脳研究
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Academic Significance and Societal Importance of the Research Achievements |
統合失調症は人口の1%弱が罹患し比較的頻度が高く、再発・慢性化しやすい精神疾患で社会経済的負担が大きいが、未だ発症の分子メカニズムは解明されておらず、根本的治療の実現には至っていない。統合失調症の主要な病態仮説の1つに、NMDA受容体機能低下仮説があるがそのメカニズムは未解明である。過去の知見から統合失調症患者においてプロリン代謝経路亢進からグルタミン酸産生過剰を招き二次的にNMDA受容体機能低下につながる可能性が示唆され、今回の研究はそのメカニズム解明に寄与できると考えられ、この知見はドパミン仮説に基づく既存の抗精神病薬とは異なる新規の観点からの創薬につながる可能性があり独創的なものである。
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