Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders.
Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders.
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枫糖浆尿液疾病中的大脑分支链氨基酸：神经系统疾病的影响。
DOI：
10.3390/ijms21207490
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发表时间：
2020-10-11
影响因子：
5.6
通讯作者：
Ahrens-Nicklas RC
中科院分区：
文献类型：
--
作者：
Xu J;Jakher Y;Ahrens-Nicklas RC
枫糖尿病是一种常染色体隐性遗传病，由支链α-酮酸脱氢酶复合体活性降低所致，催化支链氨基酸的不可逆分解代谢。目前对这种BCAA代谢紊乱的治疗包括限制BCAA的饮食和肝移植，其目的是部分恢复外周BCKDC的功能活性。这些治疗改善了支链氨基酸的循环水平，显著提高了MSUD患者的存活率。然而，严重的认知和精神疾病仍然存在。具体地说，患者一生中患认知障碍、情绪和焦虑症(抑郁、焦虑和惊恐障碍)以及注意力缺陷障碍的风险更高。最近的文献表明，神经后遗症可能是由于支链氨基酸在大脑中的特定作用。这篇综述将集中在MSUD患者大脑中观察到的支链氨基酸的紊乱，并将探索导致神经功能障碍的潜在机制。最后，我们将讨论最近的证据，暗示支链氨基酸代谢与其他神经疾病的相关性。了解支链氨基酸在中枢神经系统中的作用可能有助于未来确定MSUD和广泛的神经疾病的新治疗方法。
Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.
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