Molecular Mechanisms underlying a novel form of cell death induced by impaired GDNF signaling

对GDNF剥夺（CI DEN）引发的肠神经元caspase非依赖性细胞死亡的分子机制的研究发现，肠神经元中Apaf-1功能的内在缺失，这可能是CIDEN缺乏细胞凋亡形态学标志的原因。在体内阻断CIDEN的基因操作不会引起肠道神经元数量的增加，这表明CIDEN在生理条件下不会发生。然而，在先天性巨结肠疾病（HSCR，先天性肠神经节缺失）的小鼠模型中，阻断CIDEN可挽救肠神经节病，这表明CIDEN是HSCR发病机制的核心。

Investigation of molecular mechanism underlying caspase-independent cell death of enteric neurons triggered by GDNF deprivation(CI DEN) revealed an intrinsic absence of Apaf-1 function in enteric neurons, which appears to account for the lack in morphological hallmark of apoptosis in CIDEN. Genetic manipulation to block CIDEN in vivo did not cause an increased numbers of enteric neurons, suggesting that CIDEN does not occur in the physiological condition. Blocking CIDEN, however, rescued the intestinal aganglionosis in a mouse model for Hirschsprung disease(HSCR, congenital absence of the enteric ganglia), suggesting that CIDEN is central to the pathogenesis of HSCR.