Department of Neurochemistry, NY State Institute for Basic Research in Developmental Disabilities, New York, New York 10314, USA.
J Neurosci Res. 2010 Sep;88(12):2641-7. doi: 10.1002/jnr.22416.
Although the pathogenesis of autism is not understood, emerging evidence points to apoptotic mechanisms being involved in this disorder. However, it is not known whether apoptosis signaling is deregulated in the brain of autistic subjects. This study investigates how the apoptosis-related proteins are regulated in the autistic brain. Our studies show that Bcl2 is significantly decreased, whereas the expression of p53 is increased, in the brain of autistic subjects in comparison with age-matched controls. We also found that the expression and phosphorylation/activation of Akt kinase that regulates Bcl2 are significantly decreased in the autistic brain. The down-regulation of Akt may result from a decreased concentration of brain-derived neurotrophic factor (BDNF), the growth factor that modulates Akt activities. These results suggest that down-regulation of the BDNF-Akt-Bcl2 antiapoptotic signaling pathway in the autistic brain could be one of the underlying mechanisms responsible for the pathogenesis of autism.
虽然自闭症的发病机制尚不清楚，但新出现的证据表明凋亡机制与此类疾病有关。然而，目前尚不清楚凋亡信号是否在自闭症患者的大脑中失调。本研究旨在探讨与凋亡相关的蛋白在自闭症大脑中的调控情况。我们的研究结果表明，与年龄匹配的对照组相比，自闭症患者大脑中的 Bcl2 明显减少，而 p53 的表达则增加。我们还发现，调节 Bcl2 的凋亡相关蛋白激酶 Akt 的表达和磷酸化/激活明显减少。Akt 的下调可能是由于脑源性神经营养因子（BDNF）浓度降低所致，BDNF 是调节 Akt 活性的生长因子。这些结果表明，自闭症患者大脑中 BDNF-Akt-Bcl2 抗凋亡信号通路的下调可能是自闭症发病机制的一个潜在机制。
