Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, CHU Poitiers, University of Poitiers, Poitiers, France.
Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, University of Poitiers, 11 Boulevard Marie et Pierre Curie, Poitiers, France.
Mol Brain. 2018 Jan 4;11(1):1. doi: 10.1186/s13041-017-0343-6.
Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). The aerobic glycolysis consists to a supply of a large part of glucose into lactate regardless of oxygen. Aerobic glycolysis is less efficient in terms of ATP production than oxidative phosphorylation because of the shunt of the TCA cycle. Dysregulation of energetic metabolism might promote cell deregulation and progression of ASD. Warburg effect regulation could be an attractive target for developing therapeutic interventions in ASD.
自闭症谱系障碍（ASD）是一种神经发育疾病，其特征是社交互动和沟通能力缺陷，以及重复和受限的行为。在改变的细胞中，代谢酶会被经典 WNT/β-连环蛋白途径的失调所修饰。在 ASD 中，经典 WNT/β-连环蛋白途径被上调。我们专注于这个假说，即在 ASD 中，经典 WNT/β-连环蛋白途径的过表达会刺激瓦伯格效应。WNT/β-连环蛋白途径的上调通过激活葡萄糖转运蛋白 (Glut)、丙酮酸激酶 M2 (PKM2)、丙酮酸脱氢酶激酶 1(PDK1)、单羧酸转运蛋白 1 (MCT-1)、乳酸脱氢酶激酶-A (LDH-A) 和抑制丙酮酸脱氢酶复合物 (PDH) 诱导有氧糖酵解，称为瓦伯格效应。有氧糖酵解是指将大部分葡萄糖转化为乳酸，而与氧气无关。有氧糖酵解在 ATP 产生方面的效率低于氧化磷酸化，因为三羧酸循环的分流。能量代谢的失调可能会促进细胞失调和 ASD 的进展。瓦伯格效应的调节可能是开发 ASD 治疗干预措施的一个有吸引力的目标。
