Griffith Health Institute and School of Medical Sciences, Griffith University, Parklands Drive, Southport, QLD 4215, Australia.
Alcohol Clin Exp Res. 2011 Jun;35(6):1041-9. doi: 10.1111/j.1530-0277.2011.01436.x. Epub 2011 Feb 17.
Neuropathological damage as a result of chronic alcohol abuse often results in the impairment of cognitive function. The damage is particularly marked in the frontal cortex. The 14-3-3 protein family consists of 7 proteins, β, γ, ε, ζ, η, θ, and σ, encoded by 7 distinct genes. They are highly conserved molecular chaperones with roles in the regulation of metabolism, signal transduction, cell-cycle control, protein trafficking, and apoptosis. They may also play an important role in neurodegeneration in chronic alcoholism.
We used real-time PCR to measure the expression of 14-3-3 mRNA transcripts in both the dorsolateral prefrontal cortex and motor cortex of human brains obtained at autopsy.
We found significantly lower 14-3-3β, γ, and θ expression in both cortical areas of alcoholics, but no difference in 14-3-3η expression, and higher expression of 14-3-3σ in both areas. Levels of 14-3-3ζ and ε transcripts were significantly lower only in alcoholic motor cortex.
Altered 14-3-3 expression could contribute to synaptic dysfunction and altered neurotransmission in chronic alcohol misuse by human subjects.
慢性酒精滥用导致的神经病理学损伤通常会导致认知功能受损。这种损伤在额叶皮层尤为明显。14-3-3 蛋白家族由 7 种蛋白质组成，β、γ、ε、ζ、η、θ 和 σ，由 7 个不同的基因编码。它们是高度保守的分子伴侣，在代谢调节、信号转导、细胞周期控制、蛋白质运输和细胞凋亡中发挥作用。它们在慢性酒精中毒中的神经退行性变中也可能发挥重要作用。
我们使用实时 PCR 测量了尸检获得的人类大脑背外侧前额叶皮层和运动皮层中 14-3-3 mRNA 转录本的表达。
我们发现酒精中毒患者两个皮质区的 14-3-3β、γ 和 θ 表达明显降低，但 14-3-3η 的表达没有差异，两个区的 14-3-3σ 表达升高。只有在酒精性运动皮层中，14-3-3ζ 和 ε 转录本的水平明显降低。
改变的 14-3-3 表达可能导致人类慢性酒精滥用时的突触功能障碍和神经递质传递改变。
