Of mice and men: Plasma phenylalanine reduction in PKU corrects neurotransmitter pathways in the brain

被引：14

作者：

Berguig, Geoffrey Y. ^{[1
]}

Martin, Nathan T. ^{[1
]}

Creer, Athena Y. ^{[1
]}

Xie, Lin ^{[1
]}

Zhang, Lening ^{[1
]}

Murphy, Ryan ^{[1
]}

Pacheco, Glenn ^{[1
]}

Bullens, Sherry ^{[1
]}

Olbertz, Joy ^{[1
]}

Weng, Haoling H. ^{[1
]}

机构：

[1] BioMarin Pharmaceut Inc, 105 Digital Dr, Novato, CA 94949 USA

来源：

MOLECULAR GENETICS AND METABOLISM | 2019年 / 128卷 / 04期

关键词：

Phenylketonuria; Neurotransmitters; Biomarkers; PKU; Pegvaliase; PHENYLKETONURIA; DOPAMINE; ADULTS; ATOMOXETINE; TRYPTOPHAN; SEROTONIN; SYMPTOMS; DISORDER; BEHAVIOR; ACID;

D O I：

10.1016/j.ymgme.2019.08.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In phenylketonuria (PKU), mutations of the phenylalanine hydroxylase (PAH) gene decrease the ability of PAH to convert phenylalanine (Phe) to tyrosine (Tyr), resulting in Phe accumulation in the blood and brain and disruption of neurotransmitter (NT) biosynthesis and metabolism. The following translational study explored the relationship between pegvaliase-mediated Phe correction in plasma and the NT biosynthesis and metabolism pathway in mice and humans with PKU. Lower plasma Phe levels were associated with normalization of the NT biosynthesis pathway which correlated with an improvement in inattention symptoms in subjects with PKU.

引用

页码：422 / 430

页数：9

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