Child Neurology and Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy.
Referral Centre for Inborn Metabolic Diseases, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2019 Apr 16;20(8):1878. doi: 10.3390/ijms20081878.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交沟通和互动缺陷，以及受限、重复的行为，具有复杂的、多因素的病因。尽管 ASD 的全球患病率不断上升，但目前尚无药物治疗方法可治疗 ASD 的核心症状。临床证据和分子数据支持线粒体脂肪酸氧化（FAO）受损在 ASD 中的作用。认识到 ASD 中的能量代谢缺陷可能对更好地理解 ASD 和开发治疗干预措施很重要。核过氧化物酶体增殖物激活受体（PPAR）α、δ 和 γ 是配体激活的受体，在调节脂质和葡萄糖代谢以及炎症反应方面具有不同的生理功能。PPAR 的激活允许许多 FAO 酶的协调上调，导致线粒体 FAO 通量的显著 PPAR 驱动增加。白藜芦醇（RSV）是一种多酚化合物，具有代谢、抗氧化和抗炎特性，这表明它在 ASD 治疗中有潜在的应用。在这项研究中，我们回顾了 ASD 与受损的线粒体 FAO 之间现有联系的证据，并回顾了 PPAR 激活剂（包括 RSV）调节 ASD 中线粒体 FAO 的潜在意义。
