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Dr. J. Jay Gargus, Ian Parker and colleagues at the UCI Center for 自闭症 研究 & Translation examined skin biopsies of patients with three very different genetic types of the disorder (fragile X syndrome and tuberous sclerosis 1 and 2). They discovered that a cellular calcium signaling process involving the inositol trisphosphate receptor was very much altered.

J. Jay Gargus
“We believe this finding will be another arrow in the quiver for early and accurate diagnoses of autism spectrum disorders,” said Dr. J. Jay Gargus, director of the Center for 自闭症 研究 & Translation.
信用:史蒂夫zylius /威尼斯棋牌欧文分校的通信

此IP3R功能缺陷定位于内质网,它是在细胞的细胞器称为专门膜隔室中,并且可以支撑认知障碍 - 以及可能的消化和免疫问题 - 与孤独症有关。

“We believe this finding will be another arrow in the quiver for early and accurate diagnoses of autism spectrum disorders,” said Gargus, director of the Center for 自闭症 研究 & Translation and professor of pediatrics and physiology & biophysics. “Equally exciting, it also presents a target of a molecular class already well-established to be useful for drug discovery.”

研究结果显示在线 在平移精神病学,一个性质的出版物。

自闭症谱系障碍是影响美国的2%的范围内复杂的神经发育障碍的儿童。 ASD的社会和经济负担是巨大的,目前估计在美国超过十亿$ 66%的年单独。药物开发已被证明存在问题由于ASD的根本原因的了解有限,最近的一些备受期待的药物试验失败所证明。




在IP3R控制钙从ER释放。在大脑中,钙用于内和神经元之间的通信的信息,并且它激活的其他细胞功能,包括那些调节学习和记忆,神经元兴奋性和神经递质释放的宿主 - 已知在ASD功能失调的区域。

“We propose that the proper function of this channel and its signaling pathway is critical for normal performance of neurons and that this signaling pathway represents a key ‘hub’ in the pathogenesis of ASD,” said Parker, a fellow of London’s Royal Society and 威尼斯棋牌欧文分校 professor of neurobiology & behavior, who studies cellular calcium signaling.

看是否IP3R功能是在整个自闭症谱系改变,临床研究 Center for 自闭症 & Neurodevelopmental Disorders — which is affiliated with the Center for 自闭症 研究 & Translation — are currently expanding the study and have begun to examine children with and without typical ASD for the same signaling abnormalities. These patients undergo complete behavioral diagnostic testing, and sophisticated EEG, sleep and biochemical studies are performed. This includes the sequencing of their entire genome. Also, skin cell samples are cultured and made available to lab-based researchers for functional assays.

In the area of drug discovery, scientists at the Center for 自闭症 研究 & Translation continue to probe the IP3R channel, specifically how it regulates the level of neuron excitability. The brains of people who have autism show signs of hyperexcitability, which is also seen in epilepsy, a disorder increasingly found to be associated with ASD. Cells from individuals who have autism exhibit depressed levels of calcium signaling, and this might explain why these patients experience this hyperexcitability. By restoring the release of calcium from the IP3R, the researchers believe, they can apply a “brake” on this activity.

Galina Schmunk, Bryan Boubion and Ian Smith of 威尼斯棋牌欧文分校 contributed to the study, which received support from the National Institutes of 健康 (grants GM048071 and GM1000201) and the William & Nancy Thompson Family Foundation. The discovery is being patented by the 美国威尼斯棋牌 as a diagnostic tool and for identifying potential therapeutic agents.