Department of Neurology, Renmin hospital of Wuhan University, Wuhan, 430060, China.
BMC Neurol. 2022 May 2;22(1):166. doi: 10.1186/s12883-022-02694-2.
Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.
溶血磷脂酸（LPA）是一种常见的甘油磷脂，也是一种重要的细胞外信号分子。LPA 与受体结合并介导多种生物学效应，包括缺血性脑损伤和创伤性脑损伤的病理生理过程。然而，介导 LPA 病理作用的分子机制尚不清楚。在这里，我们发现 LPA 激活了周期蛋白依赖性激酶 5（CDK5）。CDK5 磷酸化 tau，导致神经元细胞死亡。抑制 LPA 的产生或阻断其受体减少了 CDK5 的异常激活和 tau 的磷酸化，从而逆转了神经元的死亡。我们的数据表明，LPA-CDK5-Tau 通路在缺血性中风后的病理生理过程中起着重要作用。抑制 LPA 通路可能是治疗缺血性脑损伤的潜在治疗靶点。
