2023年9月30日、「ドコサヘキサエン酸/アラキドン酸比に関連する脂質過酸化と自閉スペクトラム障害の社会的行動とフェロプトーシス」に関する原著論文がInternational Journal of Molecular Sciences (Impact Factor 5.6:Q1) に掲載されました。本研究は千葉大学との共同研究です。

　現代医学では自閉症の原因となるバイオマーカーは分かっていません。我々は自閉症児における脂質代謝系の異常に着目し、分子生物学的手法からその病態を解明してきました。本研究の知見をもとに、自閉症児の未来に向けた新薬の開発に結び付けたいと願っています。

PDF Version: https://www.mdpi.com/1422-0067/24/19/14796/pdf 

HP: https://www.mdpi.com/1422-0067/24/19/14796

Abstract 

Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls. Social behaviors were assessed using the social responsiveness scale (SRS). To overcome the problem of using small samples, adaptive Lasso was used to enhance the interpretability accuracy, and a coefficient of variation was used for variable selections. Plasma levels of the MDA-LDL levels (91.00 ± 16.70 vs. 74.50 ± 18.88) and the DHA/arachidonic acid (ARA) ratio (0.57 ± 0.16 vs. 0.37 ± 0.07) were significantly higher and the superoxide dismutase levels were significantly lower in the ASD group than those in the control group. Total SRS scores in the ASD group were significantly higher than those in the control group. The unbeneficial DHA/ARA ratio induced ferroptosis via lipid peroxidation. Multiple linear regression analysis and adaptive Lasso revealed an association of the DHA/ARA ratio with total SRS scores and increased MDA-LDL levels in plasma, resulting in neuronal deficiencies. This unbeneficial DHA/ARA-ratio-induced ferroptosis contributes to autistic social behaviors and is available for therapy.