2023 Fiscal Year Final Research Report
Establishment of a system to evaluate the Parkinson's disease-inducing potential of chemicals considering genetic predisposition
| Project/Area Number |
22K17344
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | パーキンソン病 / 環境要因 / ドパミン神経細胞 / ミトコンドリア / グルコース |
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| Outline of Final Research Achievements |
In this study, we confirmed that the human mesencephalic-derived cell line LUHMES cells exhibit dopaminergic neuron-like phenotypes by inducing differentiation, and examined the conditions under which these cells were exposed to the mitochondrial neurotoxin MPP+. As a first step in identifying glucose utilization-related genes that control sensitivity to mild mitochondrial dysfunction, we extracted genes that show characteristic expression patterns in dopaminergic neurons. However, problems with the culture of LUHMES cells arose, and the evaluation system could not be established. On the other hand, although not initially planned, analysis using human neuroblastoma SH-SY5Y cells provided insight into the mechanism of cell death caused by both mild mitochondrial dysfunction and impaired glucose utilization.
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| Free Research Field |
神経毒性学
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| Academic Significance and Societal Importance of the Research Achievements |
近年、ゲノムワイド関連解析によりパーキンソン病（PD）の遺伝的素因（感受性遺伝子）が明らかになりつつあるが、PDの発症に強く寄与する決定的な環境要因（特に化学物質）はいまだ特定されていない。本研究では、遺伝的素因を考慮した低濃度化学物質のPD誘発リスク評価系構築には至らなかったが、その第一段階としてドパミン神経細胞において特徴的な発現パターンを示す遺伝子を抽出することができた。今後、抽出した遺伝子群の中からミトコンドリア神経毒に対する感受性を制御するグルコース利用関連遺伝子を特定し、上述の評価系を構築することができれば、PDの発症に関与する化学物質の特定につながることが期待される。
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