NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America.
PLoS One. 2011;6(8):e23751. doi: 10.1371/journal.pone.0023751. Epub 2011 Aug 31.
Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP-dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.
自闭症是一种严重的神经发育障碍，其特征是语言、沟通和社交技能受损。在退行性自闭症中，受影响的儿童最初表现出正常的社交和语言发展迹象，但最终会失去这些技能并发展出自闭症行为。蛋白激酶在 G 蛋白偶联、受体介导的信号转导中至关重要，并且参与神经元功能、基因表达、记忆和细胞分化。我们研究了蛋白激酶 A（PKA）的活性和表达，PKA 是一种环 AMP 依赖性蛋白激酶，在退行性自闭症患者的额、颞、顶和枕叶以及小脑的死后脑组织样本中；自闭症患者无临床退行病史；以及年龄匹配的发育正常的对照组。与对照组和非退行性自闭症患者相比，退行性自闭症患者的额皮质中 PKA 的活性和 PKA（C-α）的表达显著降低，PKA（C-α）是 PKA 的催化亚基。这种变化在小脑或自闭症患者的颞叶、顶叶和枕叶区域的皮质中没有观察到。此外，非退行性自闭症和对照组之间 PKA 活性或 PKA（C-α）的表达没有显著差异。这些结果表明，自闭症的退行性可能部分与 PKA 介导的蛋白磷酸化减少和细胞信号异常有关。
