Morikawa Takuya, Takahashi Masatomo, Izumi Yoshihiro, Bamba Takeshi, Moriyama Kosei, Hattori Gohsuke, Fujioka Ryuta, Miura Shiroh, Shibata Hiroki
Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Biomedicines. 2023 Apr 4;11(4):1092. doi: 10.3390/biomedicines11041092.
Hereditary spastic paraplegia is a genetic neurological disorder characterized by spasticity of the lower limbs, and spastic paraplegia type 28 is one of its subtypes. Spastic paraplegia type 28 is a hereditary neurogenerative disorder with an autosomal recessive inheritance caused by loss of function of . encodes phospholipase A1, which catalyzes phospholipids to lysophospholipids such as phosphatidic acids and phosphatidylinositols to lysophosphatidic acids and lysophoshatidylinositols. Quantitative changes in these phospholipids can be key to the pathogenesis of SPG28, even at subclinical levels. By lipidome analysis using plasma from mice, we globally examined phospholipids to identify molecules showing significant quantitative changes in knockout mice. We then examined reproducibility of the quantitative changes in human sera including SPG28 patients. We identified nine kinds of phosphatidylinositols that show significant increases in knockout mice. Of these, four kinds of phosphatidylinositols replicated the highest level in the SPG28 patient serum. All four kinds of phosphatidylinositols contained oleic acid. This observation suggests that the amount of oleic acid-containing PI was affected by loss of function of DDHD1. Our results also propose the possibility of using oleic acid-containing PI as a blood biomarker for SPG28.
遗传性痉挛性截瘫是一种遗传性神经系统疾病，其特征为下肢痉挛，28型痉挛性截瘫是其中一种亚型。28型痉挛性截瘫是一种常染色体隐性遗传的遗传性神经退行性疾病，由……功能丧失引起。……编码磷脂酶A1，该酶催化磷脂生成溶血磷脂，如将磷脂酸和磷脂酰肌醇催化生成溶血磷脂酸和溶血磷脂酰肌醇。这些磷脂的定量变化可能是SPG28发病机制的关键，即使在亚临床水平也是如此。通过对小鼠血浆进行脂质组分析，我们全面检测了磷脂，以鉴定在……基因敲除小鼠中显示出显著定量变化的分子。然后，我们检测了包括SPG28患者在内的人类血清中定量变化的可重复性。我们鉴定出9种在……基因敲除小鼠中显著增加的磷脂酰肌醇。其中，4种磷脂酰肌醇在SPG28患者血清中重现了最高水平。所有4种磷脂酰肌醇都含有油酸。这一观察结果表明，含油酸的磷脂酰肌醇的量受DDHD1功能丧失的影响。我们的结果还提出了将含油酸的磷脂酰肌醇用作SPG28血液生物标志物的可能性。
