Docosahexaenoic acid (DHA) is one of the most important fatty acids that plays a critical role in maintaining proper brain function and cognitive development. Deficiency of DHA leads to several neurodegenerative disorders and, therefore, dietary supplementations of these fatty acids are essential to maintain cognitive health. However, the complete picture of how DHA is incorporated into the brain is yet to be explored. In general, the de novo synthesis of DHA is poor, and targeting the brain with specific phospholipid carriers provides novel insights into the process of reduction of disease progression. Recent studies have suggested that compared to triacylglycerol form of DHA, esterified form of DHA (i.e., lysophosphatidylcholine [lysoPC]) is better incorporated into the brain. Free DHA is transported across the outer membrane leaflet of the blood-brain barrier via APOE4 receptors, whereas DHA-lysoPC is transported across the inner membrane leaflet of the blood-brain barrier via a specific protein called Mfsd2a. Dietary supplementation of this lysoPC specific form of DHA is a novel therapy and is used to decrease the risk of various neurodegenerative disorders. Currently, structured glycerides of DHA - novel nutraceutical agents - are being widely used for the prevention and treatment of various neurological diseases. However, it is important to fully understand their metabolic regulation and mechanism of transportation to the brain. This article comprehensively reviews various studies that have evaluated the bioavailability of DHA, mechanisms of DHA transport, and role of DHA in preventing neurodegenerative disorders, which provides better insight into the pathophysiology of these disorders and use of structured DHA in improving neurological health.

中文翻译：

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DHA 的结构形式可预防神经退行性疾病：更好地了解 DHA 转运至大脑的病理生理学和机制

二十二碳六烯酸 (DHA) 是最重要的脂肪酸之一，在维持适当的大脑功能和认知发展方面起着至关重要的作用。DHA 缺乏会导致多种神经退行性疾病，因此，这些脂肪酸的膳食补充剂对于维持认知健康至关重要。然而，DHA 如何融入大脑的完整图景尚待探索。一般来说，DHA 的从头合成很差，用特定的磷脂载体靶向大脑为减缓疾病进展的过程提供了新的见解。最近的研究表明，与 DHA 的三酰基甘油形式相比，酯化形式的 DHA（即溶血磷脂酰胆碱 [lysoPC]）更好地融入大脑。游离 DHA 通过 APOE4 受体跨血脑屏障的外膜小叶运输，而 DHA-lysoPC 通过称为 Mfsd2a 的特定蛋白质跨血脑屏障的内膜小叶运输。这种 lysoPC 特定形式的 DHA 的膳食补充剂是一种新疗法，用于降低各种神经退行性疾病的风险。目前，DHA 的结构化甘油酯——一种新型的营养药物——被广泛用于预防和治疗各种神经系统疾病。然而，充分了解它们的代谢调节和向大脑运输的机制很重要。本文全面回顾了各种评估 DHA 生物利用度、DHA 转运机制以及 DHA 在预防神经退行性疾病中的作用的研究，